Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Type 2, Drug Therapy, Diabetes Mellitus, Non Insulin Dependent, Glucose Intolerance, Hyperglycemia
Brief summary
The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.
Detailed description
Over the past 30 years, the prevalence of diabetes has increased dramatically throughout the world due to population growth, aging, urbanization, increasing obesity, and physical inactivity. The total number of people with type 2 diabetes mellitus is projected to rise from 171 million in 2000 to 366 million in 2030. The incidence of type 2 diabetes mellitus in the United States alone is expected to increase from approximately 17 to 30.3 million by the year 2030. Type 2 diabetes mellitus is associated with a number of long-term microvascular and macrovascular complications associated with a reduced quality of life and increased morbidity and mortality. It is anticipated that the increasing incidence of type 2 diabetes mellitus will place an ever-increasing burden on families, increase national expenditures for health care services, and decrease worker productivity. Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha-glucosidase, analogs of glucagon-like peptide-1 and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have achieving the target glycosylated hemoglobin level less than 7%. SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion) and pioglitazone (enhancement of insulin sensitivity), the goal of this study is to evaluate the efficacy of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on metformin. Study participation is anticipated to be approximately 7 months.
Interventions
DRUGAlogliptin
Alogliptin tablets.
Alogliptin placebo-matching tablets.
DRUGPioglitazone
Pioglitazone tablets.
Pioglitazone placebo-matching tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Men or women with a historical diagnosis of type 2 diabetes mellitus who were treated with metformin greater than or equal to 1500 mg alone but were experiencing inadequate glycemic control. * A stable dose of metformin of greater than or equal to 1500 mg or maximum tolerated dose. * No treatment with antidiabetic agents other than metformin within the 2 months prior to Screening. * A body mass index greater than or equal to 23 kg/m\^2 and less than or equal to 45 kg/m\^2. * Fasting C-peptide greater than or equal to 0.8 ng/mL. * Regular use of other, non-excluded medications was allowed if a stable dose had been established for at least 4 weeks prior to Screening. * Systolic blood pressure less than or equal to 160 mmHg and diastolic pressure less than or equal to 100 mmHg. * Hemoglobin greater than or equal to 12 g/dL for men and greater than or equal to 10 g/dL for women. * Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal. * Serum creatinine less than 1.5 mg/dL for men and less than 1.4 mg/dL for women. * Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject was clinically euthyroid. * Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. * Able and willing to monitor their own blood glucose concentrations with a home glucose monitor. * No major illness or debility that in the investigator's opinion prohibited the patient from completing the study.
Exclusion criteria
* Urine albumin/creatinine ratio greater than 113 mg/mmol at Screening. * A history of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 5 years prior to Screening. * A history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening. * A history of treated diabetic gastroparesis. * New York Heart Association Class III or IV heart failure regardless of therapy. * History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening. * History of any hemoglobinopathy. * History of infection with hepatitis B, hepatitis C or human immunodeficiency virus. * History of a psychiatric disorder that could have affected the patient's ability to participate in the study. * History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors. * A history of alcohol or substance abuse within 2 years prior to Screening. * Receipt of any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening. * Previous participation in an investigational study of alogliptin. * Hypersensitive to pioglitazone, alogliptin, or other excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) | Baseline and Week 26 | The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone). |
| Change From Baseline to Week 26 in HbA1c | Baseline and Week 26 | The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in HbA1c | Baseline and Week 8 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates. |
| Change From Baseline to Week 12 in HbA1c | Baseline and Week 12 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates. |
| Change From Baseline to Week 16 in HbA1c | Baseline and Week 16 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates. |
| Change From Baseline to Week 20 in HbA1c | Baseline and Week 20 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates. |
| Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26. | The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 1 in Fasting Plasma Glucose | Baseline and Week 1 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 2 in Fasting Plasma Glucose | Baseline and Week 2 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 4 in Fasting Plasma Glucose | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 8 in Fasting Plasma Glucose | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 12 in Fasting Plasma Glucose | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 16 in Fasting Plasma Glucose | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 20 in Fasting Plasma Glucose | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Change From Baseline to Week 26 in Fasting Plasma Glucose | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates. |
| Percentage of Participants With Marked Hyperglycemia (Grouped Analysis) | From Week 1 to Week 26 | Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With Marked Hyperglycemia | From Week 1 to Week 26 | Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). |
| Percentage of Participants Meeting Rescue Criteria (Grouped Analysis) | From Week 1 to Week 26. | Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: 1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; 4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c. |
| Percentage of Participants Meeting Rescue Criteria | From Week 1 to Week 26 | Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: 1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; 4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis) | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis) | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis) | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis) | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis) | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis) | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis) | Baseline and Week 26. | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%. |
| Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates. |
| Change From Baseline to Week 4 in Fasting Proinsulin | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline to Week 20 in Insulin Levels | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 8 in Fasting Proinsulin | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline to Week 12 in Fasting Proinsulin | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline to Week 16 in Fasting Proinsulin | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline to Week 20 in Fasting Proinsulin | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline to Week 26 in Fasting Proinsulin | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates. |
| Change From Baseline in Insulin Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 4 in Insulin Levels | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 8 in Insulin Levels | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 12 in Insulin Levels | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 16 in Insulin Levels | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline to Week 26 in Insulin Levels | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates. |
| Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | Baseline and Week 4 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | Baseline and Week 8 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | Baseline and Week 12 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | Baseline and Week 16 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | Baseline and Week 20 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | Baseline and Week 26 | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates. |
| Change From Baseline in C-peptide Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 4 in C-peptide Levels | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 8 in C-peptide Levels | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 12 in C-peptide Levels | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 16 in C-peptide Levels | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 20 in C-peptide Levels | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline to Week 26 in C-peptide Levels | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates. |
| Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 4 in Total Cholesterol Levels | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 8 in Total Cholesterol Levels | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 12 in Total Cholesterol Levels | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 16 in Total Cholesterol Levels | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 20 in Total Cholesterol Levels | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline to Week 26 in Total Cholesterol Levels | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates. |
| Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates. |
| Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates. |
| Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 4 in Triglyceride Levels | Baseline and Week 4 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 8 in Triglyceride Levels | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 12 in Triglyceride Levels | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 16 in Triglyceride Levels | Baseline and Week 16 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 20 in Triglyceride Levels | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline to Week 26 in Triglyceride Levels | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates. |
| Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates. |
| Change From Baseline to Week 12 in Free Fatty Acids | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates. |
| Change From Baseline to Week 26 in Free Fatty Acids | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates. |
| Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates. |
| Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates. |
| Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates. |
| Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates. |
| Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates. |
| Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates. |
| Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates. |
| Change From Baseline to Week 12 in Adiponectin | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates. |
| Change From Baseline to Week 26 in Adiponectin | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates. |
| Change From Baseline in Body Weight Over Time (Grouped Analysis) | Baseline and Weeks 8, 12, 20 and 26. | Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates. |
| Change From Baseline to Week 8 in Body Weight | Baseline and Week 8 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates. |
| Change From Baseline to Week 12 in Body Weight | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates. |
| Change From Baseline to Week 20 in Body Weight | Baseline and Week 20 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates. |
| Change From Baseline to Week 26 in Body Weight | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates. |
| Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Baseline and Weeks 12 and 26. | HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates. |
| Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | Baseline and Week 12 | The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates. |
| Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | Baseline and Week 26 | The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates. |
| Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Baseline and Weeks 12 and 26 | The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates. |
| Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | Baseline and Week 12 | The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates. |
| Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | Baseline and Week 26 | The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates. |
| Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates. |
| Change From Baseline to Week 12 in Apolipoprotein A1 | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates. |
| Change From Baseline to Week 26 in Apolipoprotein A1 | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates. |
| Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates. |
| Change From Baseline to Week 12 in Apolipoprotein A2 | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates. |
| Change From Baseline to Week 26 in Apolipoprotein A2 | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates. |
| Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates. |
| Change From Baseline to Week 12 in Apolipoprotein B | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates. |
| Change From Baseline to Week 26 in Apolipoprotein B | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates. |
| Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates. |
| Change From Baseline to Week 12 in Apolipoprotein C-III | Baseline and Week 12 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates. |
| Change From Baseline to Week 26 in Apolipoprotein C-III | Baseline and Week 26 | Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates. |
| Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates. |
| Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | Baseline and Week 12 | NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates. |
| Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | Baseline and Week 26 | NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates. |
| Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates. |
| Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Baseline and Week 12 | The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates. |
| Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Baseline and Week 26 | The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates. |
| Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates. |
| Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | Baseline and Week 12 | The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates. |
| Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | Baseline and Week 26 | The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates. |
| Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates. |
| Change From Baseline to Week 12 in VLDL Particles | Baseline and Week 12 | The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates. |
| Change From Baseline to Week 26 in VLDL Particles | Baseline and Week 26 | The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates |
| Change From Baseline in HbA1c Over Time (Grouped Analysis) | Baseline and Weeks 4, 8, 12, 16 and 20. | The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates. |
| Change From Baseline to Week 12 in Mean VLDL Particle Size | Baseline and Week 12 | The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates. |
| Change From Baseline to Week 26 in Mean VLDL Particle Size | Baseline and Week 26 | The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates. |
| Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates. |
| Change From Baseline to Week 12 in IDL Particles | Baseline and Week 12 | The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates. |
| Change From Baseline to Week 26 in IDL Particles | Baseline and Week 26 | The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates. |
| Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates. |
| Change From Baseline to Week 12 in LDL Particles | Baseline and Week 12 | The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates. |
| Change From Baseline to Week 26 in LDL Particles | Baseline and Week 26 | The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates. |
| Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates. |
| Change From Baseline to Week 12 in Mean LDL Particle Size | Baseline and Week 12 | The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates. |
| Change From Baseline to Week 26 in Mean LDL Particle Size | Baseline and Week 26 | The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates. |
| Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26. | The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates. |
| Change From Baseline to Week 12 in HDL Particles | Baseline and Week 12 | The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates. |
| Change From Baseline to Week 26 in HDL Particles | Baseline and Week 26 | The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates. |
| Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates. |
| Change From Baseline to Week 12 in Mean HDL Particle Size | Baseline and Week 12 | The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates. |
| Change From Baseline to Week 26 in Mean HDL Particle Size | Baseline and Week 26 | The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates. |
| Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Baseline and Weeks 12 and 26 | The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates. |
| Change From Baseline to Week 4 in HbA1c | Baseline and Week 4 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates. |
Countries
Australia, Brazil, Bulgaria, Chile, Croatia, Estonia, Guatemala, India, Israel, Latvia, Mexico, New Zealand, Peru, Romania, Russia, Serbia, South Africa, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at 327 investigative sites in 20 countries from 31 May 2006 to 17 March 2008.
Pre-assignment details
Participants with a diagnosis of type 2 diabetes who were inadequately controlled on a regimen of metformin alone were equally randomized to 1 of 12 double-blind treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. | 129 |
| Alogliptin 12.5 + Placebo Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. | 128 |
| Alogliptin 25 + Placebo Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. | 129 |
| Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. | 129 |
| Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. | 129 |
| Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. | 130 |
| Total | 1,554 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 2 | 3 | 1 | 2 | 1 | 2 | 0 | 7 | 5 | 4 |
| Overall Study | Hyperglycemic Rescue | 41 | 18 | 16 | 13 | 6 | 5 | 19 | 6 | 6 | 11 | 3 | 2 |
| Overall Study | Lost to Follow-up | 4 | 2 | 2 | 4 | 0 | 2 | 3 | 0 | 3 | 2 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 4 | 3 | 1 | 2 | 1 | 1 | 1 | 0 | 3 | 2 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 2 | 2 | 8 | 5 | 5 | 6 | 2 | 1 | 4 | 6 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 5 | 6 | 2 | 5 | 4 | 4 | 4 | 5 | 2 | 7 |
Baseline characteristics
| Characteristic | Alogliptin 12.5 + Placebo | Alogliptin 25 + Placebo | Placebo + Pioglitazone 15 | Alogliptin 12.5 + Pioglitazone 15 | Placebo | Alogliptin 25 + Pioglitazone 15 | Placebo + Pioglitazone 30 | Alogliptin 12.5 + Pioglitazone 30 | Alogliptin 25 + Pioglitazone 30 | Placebo + Pioglitazone 45 | Alogliptin 12.5 + Pioglitazone 45 | Alogliptin 25 + Pioglitazone 45 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 53.1 years STANDARD_DEVIATION 9.59 | 53.7 years STANDARD_DEVIATION 9.31 | 54.1 years STANDARD_DEVIATION 9.54 | 53.6 years STANDARD_DEVIATION 9.91 | 55.2 years STANDARD_DEVIATION 9.89 | 54.9 years STANDARD_DEVIATION 9.18 | 56.1 years STANDARD_DEVIATION 9.43 | 55.0 years STANDARD_DEVIATION 9.07 | 54.4 years STANDARD_DEVIATION 9.69 | 54.5 years STANDARD_DEVIATION 9.7 | 54.0 years STANDARD_DEVIATION 9.82 | 54.2 years STANDARD_DEVIATION 8.86 | 54.4 years STANDARD_DEVIATION 9.5 |
| Age, Customized <65 years | 116 participants | 112 participants | 113 participants | 109 participants | 106 participants | 112 participants | 101 participants | 111 participants | 107 participants | 112 participants | 111 participants | 112 participants | 1322 participants |
| Age, Customized ≥65 years | 12 participants | 17 participants | 17 participants | 21 participants | 23 participants | 18 participants | 28 participants | 19 participants | 23 participants | 17 participants | 19 participants | 18 participants | 232 participants |
| Baseline metformin dose | 1902.0 mg STANDARD_DEVIATION 450.17 | 1851.2 mg STANDARD_DEVIATION 413.85 | 1892.6 mg STANDARD_DEVIATION 410.7 | 1909.6 mg STANDARD_DEVIATION 418.98 | 1936.8 mg STANDARD_DEVIATION 428.41 | 1880.0 mg STANDARD_DEVIATION 413.65 | 1853.5 mg STANDARD_DEVIATION 435.72 | 1822.3 mg STANDARD_DEVIATION 444.22 | 1867.1 mg STANDARD_DEVIATION 455.48 | 1918.6 mg STANDARD_DEVIATION 417.91 | 1919.6 mg STANDARD_DEVIATION 421.22 | 1884.6 mg STANDARD_DEVIATION 439.47 | 1886.5 mg STANDARD_DEVIATION 429.08 |
| Body Mass Index (BMI) | 30.96 kg/m^2 STANDARD_DEVIATION 5.133 | 31.48 kg/m^2 STANDARD_DEVIATION 5.733 | 31.25 kg/m^2 STANDARD_DEVIATION 5.28 | 31.53 kg/m^2 STANDARD_DEVIATION 4.979 | 30.59 kg/m^2 STANDARD_DEVIATION 4.808 | 30.78 kg/m^2 STANDARD_DEVIATION 4.723 | 31.41 kg/m^2 STANDARD_DEVIATION 5.391 | 31.09 kg/m^2 STANDARD_DEVIATION 5.054 | 31.86 kg/m^2 STANDARD_DEVIATION 5.585 | 30.69 kg/m^2 STANDARD_DEVIATION 4.721 | 31.51 kg/m^2 STANDARD_DEVIATION 5.206 | 30.62 kg/m^2 STANDARD_DEVIATION 4.751 | 31.15 kg/m^2 STANDARD_DEVIATION 5.122 |
| Diabetes Duration | 6.17 years STANDARD_DEVIATION 5.614 | 5.55 years STANDARD_DEVIATION 4.879 | 5.70 years STANDARD_DEVIATION 4.767 | 6.08 years STANDARD_DEVIATION 5.485 | 6.01 years STANDARD_DEVIATION 4.958 | 6.86 years STANDARD_DEVIATION 5.489 | 7.63 years STANDARD_DEVIATION 7.069 | 5.81 years STANDARD_DEVIATION 5.054 | 6.63 years STANDARD_DEVIATION 6.005 | 5.68 years STANDARD_DEVIATION 4.232 | 6.59 years STANDARD_DEVIATION 5.273 | 6.22 years STANDARD_DEVIATION 5.014 | 6.24 years STANDARD_DEVIATION 5.375 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 60 Participants | 63 Participants | 63 Participants | 55 Participants | 63 Participants | 57 Participants | 67 Participants | 66 Participants | 62 Participants | 61 Participants | 63 Participants | 65 Participants | 745 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 66 Participants | 67 Participants | 75 Participants | 66 Participants | 73 Participants | 62 Participants | 64 Participants | 68 Participants | 68 Participants | 67 Participants | 65 Participants | 809 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 164.61 cm STANDARD_DEVIATION 10.614 | 162.38 cm STANDARD_DEVIATION 9.79 | 164.25 cm STANDARD_DEVIATION 11.007 | 164.59 cm STANDARD_DEVIATION 10.841 | 164.48 cm STANDARD_DEVIATION 10.157 | 163.74 cm STANDARD_DEVIATION 10.456 | 164.59 cm STANDARD_DEVIATION 9.724 | 163.63 cm STANDARD_DEVIATION 11.036 | 163.64 cm STANDARD_DEVIATION 9.548 | 163.14 cm STANDARD_DEVIATION 10.961 | 163.82 cm STANDARD_DEVIATION 10.708 | 163.73 cm STANDARD_DEVIATION 11.432 | 163.88 cm STANDARD_DEVIATION 10.522 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 15 Participants | 11 Participants | 9 Participants | 5 Participants | 7 Participants | 10 Participants | 5 Participants | 12 Participants | 12 Participants | 8 Participants | 12 Participants | 120 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 8 Participants | 4 Participants | 8 Participants | 3 Participants | 6 Participants | 2 Participants | 5 Participants | 9 Participants | 9 Participants | 3 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 29 Participants | 26 Participants | 20 Participants | 23 Participants | 22 Participants | 17 Participants | 15 Participants | 28 Participants | 23 Participants | 21 Participants | 22 Participants | 265 Participants |
| Race (NIH/OMB) White | 89 Participants | 80 Participants | 85 Participants | 95 Participants | 93 Participants | 96 Participants | 96 Participants | 107 Participants | 85 Participants | 85 Participants | 92 Participants | 93 Participants | 1096 Participants |
| Sex: Female, Male Female | 61 Participants | 79 Participants | 69 Participants | 70 Participants | 68 Participants | 69 Participants | 66 Participants | 76 Participants | 75 Participants | 76 Participants | 70 Participants | 78 Participants | 857 Participants |
| Sex: Female, Male Male | 67 Participants | 50 Participants | 61 Participants | 60 Participants | 61 Participants | 61 Participants | 63 Participants | 54 Participants | 55 Participants | 53 Participants | 60 Participants | 52 Participants | 697 Participants |
| Weight | 84.63 kg STANDARD_DEVIATION 19.378 | 83.25 kg STANDARD_DEVIATION 18.326 | 84.68 kg STANDARD_DEVIATION 18.634 | 85.95 kg STANDARD_DEVIATION 18.498 | 83.38 kg STANDARD_DEVIATION 18.378 | 82.90 kg STANDARD_DEVIATION 16.57 | 85.86 kg STANDARD_DEVIATION 20.347 | 83.68 kg STANDARD_DEVIATION 18.34 | 85.77 kg STANDARD_DEVIATION 18.844 | 82.10 kg STANDARD_DEVIATION 17.019 | 85.01 kg STANDARD_DEVIATION 18.536 | 82.79 kg STANDARD_DEVIATION 18.768 | 84.17 kg STANDARD_DEVIATION 18.47 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 129 | 40 / 128 | 46 / 129 | 51 / 129 | 45 / 130 | 44 / 130 | 40 / 129 | 35 / 130 | 51 / 130 | 40 / 129 | 47 / 130 | 41 / 130 |
| serious Total, serious adverse events | 2 / 129 | 5 / 128 | 6 / 129 | 1 / 129 | 2 / 130 | 1 / 130 | 2 / 129 | 3 / 130 | 6 / 130 | 10 / 129 | 2 / 130 | 5 / 130 |
Outcome results
Primary
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) | -0.89 percentage of glycosylated hemoglobin | Standard Error 0.046 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) | -1.43 percentage of glycosylated hemoglobin | Standard Error 0.046 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) | -1.42 percentage of glycosylated hemoglobin | Standard Error 0.046 |
Comparison: The null hypothesis was that the doses of alogliptin do not have any additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone. The alternative hypothesis was that at least the higher dose of alogliptin would have an additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone.p-value: <0.00195% CI: [-0.67, -0.41]ANCOVA
p-value: <0.00195% CI: [-0.66, -0.41]ANCOVA
Primary
Change From Baseline to Week 26 in HbA1c
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in HbA1c | -0.13 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in HbA1c | -0.64 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in HbA1c | -0.90 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in HbA1c | -0.75 percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in HbA1c | -1.34 percentage of glycosylated hemoglobin | Standard Error 0.078 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in HbA1c | -1.27 percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in HbA1c | -0.92 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in HbA1c | -1.39 percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in HbA1c | -1.39 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in HbA1c | -1.00 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in HbA1c | -1.55 percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in HbA1c | -1.60 percentage of glycosylated hemoglobin | Standard Error 0.08 |
p-value: <0.00195% CI: [-0.93, -0.48]ANCOVA
p-value: <0.00195% CI: [-0.81, -0.38]ANCOVA
p-value: 0.00195% CI: [-0.59, -0.15]ANCOVA
p-value: <0.00195% CI: [-0.74, -0.3]ANCOVA
p-value: <0.00195% CI: [-0.98, -0.53]ANCOVA
p-value: <0.00195% CI: [-0.7, -0.25]ANCOVA
p-value: <0.00195% CI: [-0.71, -0.27]ANCOVA
p-value: <0.00195% CI: [-0.7, -0.25]ANCOVA
p-value: <0.00195% CI: [-1.13, -0.68]ANCOVA
p-value: <0.00195% CI: [-0.77, -0.33]ANCOVA
p-value: <0.00195% CI: [-0.92, -0.48]ANCOVA
p-value: <0.00195% CI: [-0.83, -0.39]ANCOVA
Secondary
Change From Baseline in Adiponectin Over Time (Grouped Analysis)
Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 12 (n=339, 357, 348) | 6.03 μg/mL | Standard Error 0.353 |
| Pioglitazone Alone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 26 (n=356, 369, 361) | 5.98 μg/mL | Standard Error 0.396 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 12 (n=339, 357, 348) | 6.51 μg/mL | Standard Error 0.344 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 26 (n=356, 369, 361) | 6.43 μg/mL | Standard Error 0.388 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 12 (n=339, 357, 348) | 6.51 μg/mL | Standard Error 0.348 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Adiponectin Over Time (Grouped Analysis) | Week 26 (n=356, 369, 361) | 6.46 μg/mL | Standard Error 0.393 |
Secondary
Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 346) | 1.4 mg/dL | Standard Error 1 |
| Pioglitazone Alone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -1.6 mg/dL | Standard Error 1.09 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 346) | 0.2 mg/dL | Standard Error 0.98 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -1.5 mg/dL | Standard Error 1.08 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 346) | 0.3 mg/dL | Standard Error 0.99 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -2.8 mg/dL | Standard Error 1.09 |
Secondary
Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 345) | 3.1 mg/dL | Standard Error 0.26 |
| Pioglitazone Alone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 355) | 2.4 mg/dL | Standard Error 0.28 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 345) | 2.5 mg/dL | Standard Error 0.26 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 355) | 2.1 mg/dL | Standard Error 0.27 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 12 (n=339, 354, 345) | 2.3 mg/dL | Standard Error 0.26 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) | Week 26 (n=354, 367, 355) | 1.8 mg/dL | Standard Error 0.28 |
Secondary
Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis)
Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 12 (n=338, 354, 346) | -3.0 mg/dL | Standard Error 1.09 |
| Pioglitazone Alone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -2.8 mg/dL | Standard Error 1.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 12 (n=338, 354, 346) | -7.9 mg/dL | Standard Error 1.06 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -6.4 mg/dL | Standard Error 1.14 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 12 (n=338, 354, 346) | -10.0 mg/dL | Standard Error 1.07 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) | Week 26 (n=354, 367, 356) | -6.4 mg/dL | Standard Error 1.15 |
Secondary
Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis)
Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 12 (n=337, 352, 345) | -0.6 mg/dL | Standard Error 0.17 |
| Pioglitazone Alone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 26 (n=353, 366, 355) | -0.1 mg/dL | Standard Error 0.19 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 12 (n=337, 352, 345) | -1.2 mg/dL | Standard Error 0.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 26 (n=353, 366, 355) | -0.6 mg/dL | Standard Error 0.19 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 12 (n=337, 352, 345) | -1.3 mg/dL | Standard Error 0.17 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) | Week 26 (n=353, 366, 355) | -0.6 mg/dL | Standard Error 0.19 |
Secondary
Change From Baseline in Body Weight Over Time (Grouped Analysis)
Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time frame: Baseline and Weeks 8, 12, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 8 (n=361, 372, 367) | 0.45 kg | Standard Error 0.103 |
| Pioglitazone Alone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 12 (n=368, 374, 373) | 0.56 kg | Standard Error 0.125 |
| Pioglitazone Alone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 20 (n=368, 374, 373) | 1.21 kg | Standard Error 0.152 |
| Pioglitazone Alone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 26 (n=368, 374, 373) | 1.49 kg | Standard Error 0.168 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 26 (n=368, 374, 373) | 1.81 kg | Standard Error 0.167 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 8 (n=361, 372, 367) | 0.34 kg | Standard Error 0.101 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 20 (n=368, 374, 373) | 1.45 kg | Standard Error 0.151 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 12 (n=368, 374, 373) | 0.57 kg | Standard Error 0.124 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 26 (n=368, 374, 373) | 1.87 kg | Standard Error 0.167 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 12 (n=368, 374, 373) | 0.82 kg | Standard Error 0.124 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 20 (n=368, 374, 373) | 1.46 kg | Standard Error 0.151 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Body Weight Over Time (Grouped Analysis) | Week 8 (n=361, 372, 367) | 0.63 kg | Standard Error 0.102 |
Secondary
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis)
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 12 (n=347, 344, 351) | -1.832 insulin resistance | Standard Error 0.3122 |
| Pioglitazone Alone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 26 (n=348, 346, 352) | -1.571 insulin resistance | Standard Error 0.3501 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 12 (n=347, 344, 351) | -1.966 insulin resistance | Standard Error 0.3136 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 26 (n=348, 346, 352) | -2.209 insulin resistance | Standard Error 0.3512 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 12 (n=347, 344, 351) | -2.572 insulin resistance | Standard Error 0.3104 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) | Week 26 (n=348, 346, 352) | -1.711 insulin resistance | Standard Error 0.3481 |
Secondary
Change From Baseline in C-peptide Over Time (Grouped Analysis)
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 20 (n=369, 375, 375) | -0.360 ng/mL | Standard Error 0.0465 |
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 12 (n=367, 369, 374) | -0.268 ng/mL | Standard Error 0.0781 |
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 26 (n=371, 378, 375) | -0.341 ng/mL | Standard Error 0.046 |
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 4 (n=335, 335, 336) | -0.292 ng/mL | Standard Error 0.0417 |
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 16 (n=369, 374, 374) | -0.352 ng/mL | Standard Error 0.0456 |
| Pioglitazone Alone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 8 (n=367, 366, 371) | -0.356 ng/mL | Standard Error 0.0464 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 16 (n=369, 374, 374) | -0.343 ng/mL | Standard Error 0.0453 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 20 (n=369, 375, 375) | -0.350 ng/mL | Standard Error 0.0461 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 26 (n=371, 378, 375) | -0.346 ng/mL | Standard Error 0.0456 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 8 (n=367, 366, 371) | -0.327 ng/mL | Standard Error 0.0464 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 4 (n=335, 335, 336) | -0.255 ng/mL | Standard Error 0.0417 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 12 (n=367, 369, 374) | -0.249 ng/mL | Standard Error 0.0779 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 26 (n=371, 378, 375) | -0.326 ng/mL | Standard Error 0.0457 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 4 (n=335, 335, 336) | -0.282 ng/mL | Standard Error 0.0416 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 8 (n=367, 366, 371) | -0.311 ng/mL | Standard Error 0.0461 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 12 (n=367, 369, 374) | -0.334 ng/mL | Standard Error 0.0774 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 16 (n=369, 374, 374) | -0.333 ng/mL | Standard Error 0.0453 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in C-peptide Over Time (Grouped Analysis) | Week 20 (n=369, 375, 375) | -0.293 ng/mL | Standard Error 0.0461 |
Secondary
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis)
The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 2 (n=379, 383, 381) | -11.3 mg/dL | Standard Error 1.62 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 4 (n=381, 386, 383) | -19.9 mg/dL | Standard Error 1.67 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 8 (n=381, 386, 383) | -27.3 mg/dL | Standard Error 1.77 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 12 (n=381, 386, 383) | -30.3 mg/dL | Standard Error 1.84 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 16 (n=381, 386, 383) | -27.9 mg/dL | Standard Error 1.86 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 20 (n=381, 386, 383) | -28.1 mg/dL | Standard Error 2 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 26 (n=381, 386, 383) | -28.3 mg/dL | Standard Error 2.03 |
| Pioglitazone Alone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 1 (n=358, 355, 354) | -4.1 mg/dL | Standard Error 1.56 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 8 (n=381, 386, 383) | -42.3 mg/dL | Standard Error 1.76 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 26 (n=381, 386, 383) | -45.2 mg/dL | Standard Error 2.02 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 12 (n=381, 386, 383) | -45.0 mg/dL | Standard Error 1.83 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 16 (n=381, 386, 383) | -43.7 mg/dL | Standard Error 1.85 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 20 (n=381, 386, 383) | -43.6 mg/dL | Standard Error 1.99 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 2 (n=379, 383, 381) | -30.3 mg/dL | Standard Error 1.61 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 4 (n=381, 386, 383) | -36.8 mg/dL | Standard Error 1.66 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 1 (n=358, 355, 354) | -22.6 mg/dL | Standard Error 1.57 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 8 (n=381, 386, 383) | -45.2 mg/dL | Standard Error 1.77 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 4 (n=381, 386, 383) | -39.8 mg/dL | Standard Error 1.67 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 2 (n=379, 383, 381) | -31.6 mg/dL | Standard Error 1.62 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 12 (n=381, 386, 383) | -47.6 mg/dL | Standard Error 1.83 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 26 (n=381, 386, 383) | -44.2 mg/dL | Standard Error 2.03 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 20 (n=381, 386, 383) | -45.0 mg/dL | Standard Error 1.99 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 16 (n=381, 386, 383) | -45.4 mg/dL | Standard Error 1.86 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) | Week 1 (n=358, 355, 354) | -23.1 mg/dL | Standard Error 1.57 |
Secondary
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis)
Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 4 (n=328, 319, 327) | -6.2 pmol/L | Standard Error 0.81 |
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 8 (n=357, 347, 358) | -7.2 pmol/L | Standard Error 0.87 |
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 12 (n=357, 347, 358) | -8.2 pmol/L | Standard Error 0.91 |
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 16 (n=358, 348, 358) | -7.2 pmol/L | Standard Error 0.92 |
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 20 (n=358, 349, 359) | -6.6 pmol/L | Standard Error 1.08 |
| Pioglitazone Alone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 26 (n=358, 349, 359) | -5.3 pmol/L | Standard Error 1.09 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 26 (n=358, 349, 359) | -10.6 pmol/L | Standard Error 1.11 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 4 (n=328, 319, 327) | -10.3 pmol/L | Standard Error 0.82 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 16 (n=358, 348, 358) | -12.2 pmol/L | Standard Error 0.94 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 20 (n=358, 349, 359) | -10.4 pmol/L | Standard Error 1.09 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 8 (n=357, 347, 358) | -11.3 pmol/L | Standard Error 0.88 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 12 (n=357, 347, 358) | -11.6 pmol/L | Standard Error 0.93 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 8 (n=357, 347, 358) | -11.3 pmol/L | Standard Error 0.87 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 12 (n=357, 347, 358) | -11.6 pmol/L | Standard Error 0.91 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 26 (n=358, 349, 359) | -9.5 pmol/L | Standard Error 1.09 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 16 (n=358, 348, 358) | -11.3 pmol/L | Standard Error 0.92 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 4 (n=328, 319, 327) | -10.1 pmol/L | Standard Error 0.81 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) | Week 20 (n=358, 349, 359) | -10.7 pmol/L | Standard Error 1.08 |
Secondary
Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis)
Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 12 (n=339, 356, 352) | -0.0707 mmol/L | Standard Error 0.01483 |
| Pioglitazone Alone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 26 (n=353, 368, 363) | -0.0676 mmol/L | Standard Error 0.0105 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 12 (n=339, 356, 352) | -0.1306 mmol/L | Standard Error 0.01447 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 26 (n=353, 368, 363) | -0.0945 mmol/L | Standard Error 0.01029 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 12 (n=339, 356, 352) | -0.1273 mmol/L | Standard Error 0.01455 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) | Week 26 (n=353, 368, 363) | -0.1144 mmol/L | Standard Error 0.01036 |
Secondary
Change From Baseline in HbA1c Over Time (Grouped Analysis)
The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16 and 20.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 16 (n=376, 385, 377) | -0.92 percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Pioglitazone Alone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 12 (n=376, 385, 377) | -0.81 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Pioglitazone Alone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 4 (n=345, 359, 346) | -0.32 percentage of glycosylated hemoglobin | Standard Error 0.023 |
| Pioglitazone Alone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 8 (n=376, 385, 377) | -0.61 percentage of glycosylated hemoglobin | Standard Error 0.034 |
| Pioglitazone Alone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 20 (n=376, 385, 377) | -0.92 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 12 (n=376, 385, 377) | -1.29 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 4 (n=345, 359, 346) | -0.57 percentage of glycosylated hemoglobin | Standard Error 0.023 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 8 (n=376, 385, 377) | -1.06 percentage of glycosylated hemoglobin | Standard Error 0.033 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 16 (n=376, 385, 377) | -1.44 percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 20 (n=376, 385, 377) | -1.46 percentage of glycosylated hemoglobin | Standard Error 0.042 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 20 (n=376, 385, 377) | -1.51 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 16 (n=376, 385, 377) | -1.49 percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 4 (n=345, 359, 346) | -0.61 percentage of glycosylated hemoglobin | Standard Error 0.023 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 12 (n=376, 385, 377) | -1.38 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in HbA1c Over Time (Grouped Analysis) | Week 8 (n=376, 385, 377) | -1.09 percentage of glycosylated hemoglobin | Standard Error 0.034 |
Secondary
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 5.2 mg/dL | Standard Error 0.4 |
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | 4.0 mg/dL | Standard Error 0.35 |
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 5.1 mg/dL | Standard Error 0.41 |
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | 5.4 mg/dL | Standard Error 0.37 |
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 5.2 mg/dL | Standard Error 0.39 |
| Pioglitazone Alone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 353, 348) | 3.0 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 353, 348) | 2.7 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 5.7 mg/dL | Standard Error 0.4 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 5.2 mg/dL | Standard Error 0.38 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | 5.3 mg/dL | Standard Error 0.37 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 5.5 mg/dL | Standard Error 0.41 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | 4.1 mg/dL | Standard Error 0.34 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 5.0 mg/dL | Standard Error 0.41 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 353, 348) | 3.4 mg/dL | Standard Error 0.33 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | 4.6 mg/dL | Standard Error 0.35 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 5.0 mg/dL | Standard Error 0.38 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 5.2 mg/dL | Standard Error 0.4 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | 5.1 mg/dL | Standard Error 0.37 |
Secondary
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | 0.86 μMOL/L | Standard Error 0.22 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | 0.62 μMOL/L | Standard Error 0.235 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 0.89 μMOL/L | Standard Error 0.111 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 0.81 μMOL/L | Standard Error 0.123 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | 1.38 μMOL/L | Standard Error 0.195 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | 1.34 μMOL/L | Standard Error 0.195 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | -1.35 μMOL/L | Standard Error 0.261 |
| Pioglitazone Alone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | -1.45 μMOL/L | Standard Error 0.261 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 0.78 μMOL/L | Standard Error 0.109 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | -1.39 μMOL/L | Standard Error 0.256 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 0.90 μMOL/L | Standard Error 0.121 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | 1.16 μMOL/L | Standard Error 0.191 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | 1.10 μMOL/L | Standard Error 0.192 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | 0.58 μMOL/L | Standard Error 0.216 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | 1.18 μMOL/L | Standard Error 0.231 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | -0.85 μMOL/L | Standard Error 0.257 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 0.89 μMOL/L | Standard Error 0.109 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | 0.78 μMOL/L | Standard Error 0.232 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | 0.43 μMOL/L | Standard Error 0.216 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 1.01 μMOL/L | Standard Error 0.122 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | -2.12 μMOL/L | Standard Error 0.256 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | 1.46 μMOL/L | Standard Error 0.192 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | 1.63 μMOL/L | Standard Error 0.191 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | -1.73 μMOL/L | Standard Error 0.258 |
Secondary
Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis)
Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 12 (n=346, 356, 355) | -2.0274 mg/L | Standard Error 0.32717 |
| Pioglitazone Alone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 26 (n=359, 369, 363) | -0.8889 mg/L | Standard Error 0.46384 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 12 (n=346, 356, 355) | -2.4653 mg/L | Standard Error 0.32225 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 26 (n=359, 369, 363) | -1.7716 mg/L | Standard Error 0.45715 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 12 (n=346, 356, 355) | -1.9208 mg/L | Standard Error 0.32253 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) | Week 26 (n=359, 369, 363) | -0.9977 mg/L | Standard Error 0.46059 |
Secondary
Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis)
The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 12 (n=347, 344, 350) | 2.591 percentage beta cell function | Standard Error 3.7892 |
| Pioglitazone Alone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 26 (n=348, 346, 351) | 5.060 percentage beta cell function | Standard Error 3.046 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 12 (n=347, 344, 350) | 23.799 percentage beta cell function | Standard Error 3.8017 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 26 (n=348, 346, 351) | 18.173 percentage beta cell function | Standard Error 3.0522 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 12 (n=347, 344, 350) | 19.477 percentage beta cell function | Standard Error 3.7685 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) | Week 26 (n=348, 346, 351) | 22.182 percentage beta cell function | Standard Error 3.0297 |
Secondary
Change From Baseline in Insulin Over Time (Grouped Analysis)
The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 4 (n=325, 318, 326) | -2.29 µIU/mL | Standard Error 0.44 |
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 8 (n=355, 346, 356) | -2.35 µIU/mL | Standard Error 0.535 |
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 12 (n=355, 347, 356) | -2.62 µIU/mL | Standard Error 0.498 |
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 16 (n=356, 348, 356) | -2.19 µIU/mL | Standard Error 0.488 |
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 20 (n=356, 349, 357) | -2.35 µIU/mL | Standard Error 0.511 |
| Pioglitazone Alone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 26 (n=356, 349, 357) | -1.74 µIU/mL | Standard Error 1.212 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 26 (n=356, 349, 357) | -2.05 µIU/mL | Standard Error 1.225 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 4 (n=325, 318, 326) | -2.11 µIU/mL | Standard Error 0.445 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 16 (n=356, 348, 356) | -2.60 µIU/mL | Standard Error 0.494 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 20 (n=356, 349, 357) | -1.91 µIU/mL | Standard Error 0.516 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 8 (n=355, 346, 356) | -2.44 µIU/mL | Standard Error 0.542 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 12 (n=355, 347, 356) | -1.73 µIU/mL | Standard Error 0.503 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 8 (n=355, 346, 356) | -2.36 µIU/mL | Standard Error 0.534 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 12 (n=355, 347, 356) | -2.62 µIU/mL | Standard Error 0.497 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 26 (n=356, 349, 357) | -1.66 µIU/mL | Standard Error 1.21 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 16 (n=356, 348, 356) | -2.48 µIU/mL | Standard Error 0.488 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 4 (n=325, 318, 326) | -2.19 µIU/mL | Standard Error 0.44 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Insulin Over Time (Grouped Analysis) | Week 20 (n=356, 349, 357) | -2.06 µIU/mL | Standard Error 0.51 |
Secondary
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.4 nmol/L | Standard Error 2.16 |
| Pioglitazone Alone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 2.8 nmol/L | Standard Error 2.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -3.9 nmol/L | Standard Error 2.12 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -4.2 nmol/L | Standard Error 2.13 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -5.7 nmol/L | Standard Error 2.12 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -1.5 nmol/L | Standard Error 2.13 |
Secondary
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=330, 336, 338) | 3.1 mg/dL | Standard Error 1.23 |
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=365, 365, 365) | 5.9 mg/dL | Standard Error 1.28 |
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=365, 367, 366) | 6.9 mg/dL | Standard Error 1.29 |
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=365, 368, 366) | 6.1 mg/dL | Standard Error 1.29 |
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=365, 368, 366) | 6.9 mg/dL | Standard Error 1.37 |
| Pioglitazone Alone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=365, 368, 366) | 7.4 mg/dL | Standard Error 1.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=365, 368, 366) | 5.2 mg/dL | Standard Error 1.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=330, 336, 338) | -0.5 mg/dL | Standard Error 1.22 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=365, 368, 366) | 3.3 mg/dL | Standard Error 1.29 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=365, 368, 366) | 4.2 mg/dL | Standard Error 1.36 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=365, 365, 365) | 1.3 mg/dL | Standard Error 1.28 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=365, 367, 366) | 3.3 mg/dL | Standard Error 1.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 8 (n=365, 365, 365) | 0.1 mg/dL | Standard Error 1.28 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 12 (n=365, 367, 366) | 1.5 mg/dL | Standard Error 1.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 26 (n=365, 368, 366) | 5.6 mg/dL | Standard Error 1.39 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 16 (n=365, 368, 366) | 2.4 mg/dL | Standard Error 1.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 4 (n=330, 336, 338) | -1.9 mg/dL | Standard Error 1.22 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) | Week 20 (n=365, 368, 366) | 3.0 mg/dL | Standard Error 1.37 |
Secondary
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -104.1 nmol/L | Standard Error 17.46 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -78.2 nmol/L | Standard Error 17.83 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 85.5 nmol/L | Standard Error 10.02 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 95.8 nmol/L | Standard Error 11.11 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 12 (n=332, 345, 343) | -36.6 nmol/L | Standard Error 4.11 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 26 (n=348, 359, 357) | -34.3 nmol/L | Standard Error 4.22 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 12 (n=332, 345, 343) | -191.4 nmol/L | Standard Error 20.32 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 26 (n=348, 359, 357) | -178.1 nmol/L | Standard Error 21.13 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 12 (n=332, 345, 343) | -154.6 nmol/L | Standard Error 16.53 |
| Pioglitazone Alone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 26 (n=348, 359, 357) | -143.6 nmol/L | Standard Error 17.23 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 12 (n=332, 345, 343) | -232.3 nmol/L | Standard Error 16.23 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -180.5 nmol/L | Standard Error 17.13 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 26 (n=348, 359, 357) | -44.9 nmol/L | Standard Error 4.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 12 (n=332, 345, 343) | -55.3 nmol/L | Standard Error 4.03 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -146.2 nmol/L | Standard Error 17.55 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 26 (n=348, 359, 357) | -190.3 nmol/L | Standard Error 16.97 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 26 (n=348, 359, 357) | -235.0 nmol/L | Standard Error 20.81 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 111.6 nmol/L | Standard Error 9.83 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 12 (n=332, 345, 343) | -287.5 nmol/L | Standard Error 19.94 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 93.9 nmol/L | Standard Error 10.93 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 26 (n=348, 359, 357) | -285.9 nmol/L | Standard Error 20.87 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | 106.1 nmol/L | Standard Error 10.96 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 12 (n=332, 345, 343) | -60.1 nmol/L | Standard Error 4.04 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Medium-Small Particles - Week 26 (n=348, 359, 357) | -49.6 nmol/L | Standard Error 4.17 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 12 (n=332, 345, 343) | -271.3 nmol/L | Standard Error 16.27 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Small Particles - Week 12 (n=332, 345, 343) | -331.4 nmol/L | Standard Error 20 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -236.8 nmol/L | Standard Error 17.18 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Very Small Particles - Week 26 (n=348, 359, 357) | -236.2 nmol/L | Standard Error 17.02 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -182.9 nmol/L | Standard Error 17.6 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | 102.3 nmol/L | Standard Error 9.85 |
Secondary
Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.11 nm | Standard Error 0.013 |
| Pioglitazone Alone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.11 nm | Standard Error 0.015 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.13 nm | Standard Error 0.013 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.12 nm | Standard Error 0.014 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.16 nm | Standard Error 0.013 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.17 nm | Standard Error 0.014 |
Secondary
Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.43 nm | Standard Error 0.034 |
| Pioglitazone Alone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.41 nm | Standard Error 0.036 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.58 nm | Standard Error 0.034 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.47 nm | Standard Error 0.035 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | 0.61 nm | Standard Error 0.034 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | 0.54 nm | Standard Error 0.036 |
Secondary
Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis)
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 344, 343) | -2.77 nm | Standard Error 0.398 |
| Pioglitazone Alone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 358, 357) | -2.49 nm | Standard Error 0.406 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 344, 343) | -2.98 nm | Standard Error 0.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 358, 357) | -3.67 nm | Standard Error 0.4 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 12 (n=332, 344, 343) | -3.02 nm | Standard Error 0.391 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) | Week 26 (n=348, 358, 357) | -3.26 nm | Standard Error 0.4 |
Secondary
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis)
Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -19.6 mg/dL | Standard Error 3.92 |
| Pioglitazone Alone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -11.5 mg/dL | Standard Error 4.3 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -28.8 mg/dL | Standard Error 3.85 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -25.4 mg/dL | Standard Error 4.23 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -31.5 mg/dL | Standard Error 3.86 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -22.9 mg/dL | Standard Error 4.24 |
Secondary
Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis)
Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time frame: Baseline and Weeks 12 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 12 (n=311, 333, 328) | -4.14 ng/mL | Standard Error 1.97 |
| Pioglitazone Alone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 26 (n=341, 354, 348) | -4.56 ng/mL | Standard Error 2.049 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 12 (n=311, 333, 328) | -8.76 ng/mL | Standard Error 1.9 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 26 (n=341, 354, 348) | -2.69 ng/mL | Standard Error 2.01 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 12 (n=311, 333, 328) | -8.57 ng/mL | Standard Error 1.914 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) | Week 26 (n=341, 354, 348) | -9.25 ng/mL | Standard Error 2.027 |
Secondary
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis)
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 12 (n=355, 345, 356) | -0.042 ratio | Standard Error 0.0083 |
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 4 (n=325, 315, 326) | -0.021 ratio | Standard Error 0.0088 |
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 8 (n=355, 344, 356) | -0.019 ratio | Standard Error 0.0084 |
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 16 (n=356, 346, 356) | -0.033 ratio | Standard Error 0.0077 |
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 20 (n=356, 347, 357) | -0.034 ratio | Standard Error 0.0076 |
| Pioglitazone Alone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 26 (n=356, 347, 357) | -0.027 ratio | Standard Error 0.0088 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 8 (n=355, 344, 356) | -0.079 ratio | Standard Error 0.0086 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 12 (n=355, 345, 356) | -0.086 ratio | Standard Error 0.0084 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 16 (n=356, 346, 356) | -0.091 ratio | Standard Error 0.0078 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 26 (n=356, 347, 357) | -0.087 ratio | Standard Error 0.009 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 20 (n=356, 347, 357) | -0.088 ratio | Standard Error 0.0077 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 4 (n=325, 315, 326) | -0.078 ratio | Standard Error 0.0089 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 4 (n=325, 315, 326) | -0.057 ratio | Standard Error 0.0088 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 20 (n=356, 347, 357) | -0.078 ratio | Standard Error 0.0076 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 12 (n=355, 345, 356) | -0.082 ratio | Standard Error 0.0083 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 26 (n=356, 347, 357) | -0.076 ratio | Standard Error 0.0088 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 8 (n=355, 344, 356) | -0.081 ratio | Standard Error 0.0084 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) | Week 16 (n=356, 346, 356) | -0.077 ratio | Standard Error 0.0077 |
Secondary
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis)
Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | 1.6 mg/dL | Standard Error 1.41 |
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | 4.8 mg/dL | Standard Error 1.42 |
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | 6.6 mg/dL | Standard Error 1.47 |
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 6.5 mg/dL | Standard Error 1.52 |
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 5.9 mg/dL | Standard Error 1.56 |
| Pioglitazone Alone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 8.0 mg/dL | Standard Error 1.63 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 4.4 mg/dL | Standard Error 1.61 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | -4.3 mg/dL | Standard Error 1.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 1.2 mg/dL | Standard Error 1.51 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 3.0 mg/dL | Standard Error 1.55 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | -1.8 mg/dL | Standard Error 1.41 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | 1.3 mg/dL | Standard Error 1.46 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | -3.3 mg/dL | Standard Error 1.42 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | -1.7 mg/dL | Standard Error 1.46 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | 3.9 mg/dL | Standard Error 1.62 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | 0.1 mg/dL | Standard Error 1.51 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | -6.5 mg/dL | Standard Error 1.4 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | 1.5 mg/dL | Standard Error 1.56 |
Secondary
Change From Baseline in Triglycerides Over Time (Grouped Analysis)
Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | -31.5 mg/dL | Standard Error 4.07 |
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | -34.9 mg/dL | Standard Error 4.3 |
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | -34.5 mg/dL | Standard Error 4.25 |
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | -29.4 mg/dL | Standard Error 4.43 |
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | -29.6 mg/dL | Standard Error 4.42 |
| Pioglitazone Alone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | -34.7 mg/dL | Standard Error 4.37 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | -43.6 mg/dL | Standard Error 4.27 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | -38.9 mg/dL | Standard Error 4.02 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | -44.4 mg/dL | Standard Error 4.34 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | -47.5 mg/dL | Standard Error 4.21 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | -49.3 mg/dL | Standard Error 4.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | -41.4 mg/dL | Standard Error 4.39 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 16 (n=374, 380, 376) | -46.3 mg/dL | Standard Error 4.42 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 8 (n=374, 380, 376) | -47.9 mg/dL | Standard Error 4.36 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 20 (n=374, 380, 376) | -42.7 mg/dL | Standard Error 4.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 4 (n=345, 354, 348) | -48.0 mg/dL | Standard Error 4.06 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 12 (n=374, 380, 376) | -49.4 mg/dL | Standard Error 4.24 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Triglycerides Over Time (Grouped Analysis) | Week 26 (n=374, 380, 376) | -40.7 mg/dL | Standard Error 4.41 |
Secondary
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis)
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -1.85 nmol/L | Standard Error 1.803 |
| Pioglitazone Alone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -1.05 nmol/L | Standard Error 1.999 |
| Pioglitazone Alone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | -1.61 nmol/L | Standard Error 0.289 |
| Pioglitazone Alone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | -1.05 nmol/L | Standard Error 0.342 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | -2.25 nmol/L | Standard Error 0.337 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -6.40 nmol/L | Standard Error 1.77 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | -2.20 nmol/L | Standard Error 0.283 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -1.87 nmol/L | Standard Error 1.97 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 26 (n=348, 359, 357) | -1.98 nmol/L | Standard Error 0.337 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 26 (n=348, 359, 357) | -1.31 nmol/L | Standard Error 1.975 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Large Particles - Week 12 (n=332, 345, 343) | -2.17 nmol/L | Standard Error 0.284 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) | Total Particles - Week 12 (n=332, 345, 343) | -7.26 nmol/L | Standard Error 1.775 |
Secondary
Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis)
The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -20.4 mg/dL | Standard Error 3.9 |
| Pioglitazone Alone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -13.0 mg/dL | Standard Error 4.28 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -28.5 mg/dL | Standard Error 3.83 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -25.4 mg/dL | Standard Error 4.22 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 12 (n=332, 345, 343) | -30.3 mg/dL | Standard Error 3.84 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) | Week 26 (n=348, 359, 357) | -23.0 mg/dL | Standard Error 4.23 |
Secondary
Change From Baseline in VLDL Particles Over Time (Grouped Analysis)
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Time frame: Baseline and Weeks 12 and 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | 4.16 nmol/L | Standard Error 1.053 |
| Pioglitazone Alone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | -4.44 nmol/L | Standard Error 1.174 |
| Pioglitazone Alone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | 2.30 nmol/L | Standard Error 1.084 |
| Pioglitazone Alone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | -2.28 nmol/L | Standard Error 1.346 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | 1.33 nmol/L | Standard Error 1.033 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | -3.02 nmol/L | Standard Error 1.326 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | 3.55 nmol/L | Standard Error 1.067 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | -5.36 nmol/L | Standard Error 1.152 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 26 (n=348, 359, 357) | 5.22 nmol/L | Standard Error 1.07 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 12 (n=332, 345, 343) | -7.30 nmol/L | Standard Error 1.155 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Medium Particles - Week 26 (n=348, 359, 357) | -4.88 nmol/L | Standard Error 1.329 |
| Alogliptin 25 + Pioglitazone | Change From Baseline in VLDL Particles Over Time (Grouped Analysis) | Small Particles - Week 12 (n=332, 345, 343) | 1.91 nmol/L | Standard Error 1.035 |
Secondary
Change From Baseline to Week 12 in Adiponectin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Adiponectin | 0.02 μg/mL | Standard Error 0.593 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Adiponectin | 0.44 μg/mL | Standard Error 0.609 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Adiponectin | 0.22 μg/mL | Standard Error 0.606 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Adiponectin | 3.54 μg/mL | Standard Error 0.604 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Adiponectin | 3.78 μg/mL | Standard Error 0.591 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Adiponectin | 2.91 μg/mL | Standard Error 0.601 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Adiponectin | 6.07 μg/mL | Standard Error 0.617 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Adiponectin | 6.31 μg/mL | Standard Error 0.599 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Adiponectin | 7.13 μg/mL | Standard Error 0.609 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Adiponectin | 8.47 μg/mL | Standard Error 0.614 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Adiponectin | 9.42 μg/mL | Standard Error 0.598 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Adiponectin | 9.46 μg/mL | Standard Error 0.601 |
Secondary
Change From Baseline to Week 12 in Apolipoprotein A1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Apolipoprotein A1 | -1.9 mg/dL | Standard Error 1.7 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein A1 | -4.4 mg/dL | Standard Error 1.73 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein A1 | -3.0 mg/dL | Standard Error 1.74 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A1 | 0.8 mg/dL | Standard Error 1.73 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A1 | -1.3 mg/dL | Standard Error 1.69 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A1 | 1.7 mg/dL | Standard Error 1.72 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A1 | 3.5 mg/dL | Standard Error 1.72 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A1 | 0.7 mg/dL | Standard Error 1.69 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A1 | 0.4 mg/dL | Standard Error 1.69 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A1 | -0.1 mg/dL | Standard Error 1.74 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A1 | 1.1 mg/dL | Standard Error 1.71 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A1 | -1.2 mg/dL | Standard Error 1.72 |
Secondary
Change From Baseline to Week 12 in Apolipoprotein A2
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Apolipoprotein A2 | 0.4 mg/dL | Standard Error 0.44 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein A2 | 0.1 mg/dL | Standard Error 0.45 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein A2 | 0.4 mg/dL | Standard Error 0.45 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A2 | 2.4 mg/dL | Standard Error 0.45 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A2 | 1.4 mg/dL | Standard Error 0.44 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein A2 | 1.9 mg/dL | Standard Error 0.45 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A2 | 3.7 mg/dL | Standard Error 0.45 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A2 | 2.5 mg/dL | Standard Error 0.44 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein A2 | 1.8 mg/dL | Standard Error 0.44 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A2 | 3.0 mg/dL | Standard Error 0.45 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A2 | 3.7 mg/dL | Standard Error 0.45 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein A2 | 3.2 mg/dL | Standard Error 0.45 |
Secondary
Change From Baseline to Week 12 in Apolipoprotein B
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Apolipoprotein B | 5.0 mg/dL | Standard Error 1.85 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein B | -2.3 mg/dL | Standard Error 1.87 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein B | -3.6 mg/dL | Standard Error 1.89 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein B | -0.3 mg/dL | Standard Error 1.88 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein B | -7.2 mg/dL | Standard Error 1.83 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein B | -6.1 mg/dL | Standard Error 1.87 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein B | -2.1 mg/dL | Standard Error 1.88 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein B | -8.4 mg/dL | Standard Error 1.83 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein B | -12.2 mg/dL | Standard Error 1.84 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein B | -6.6 mg/dL | Standard Error 1.9 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein B | -8.0 mg/dL | Standard Error 1.86 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein B | -11.7 mg/dL | Standard Error 1.87 |
Secondary
Change From Baseline to Week 12 in Apolipoprotein C-III
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Apolipoprotein C-III | 0.7 mg/dL | Standard Error 0.28 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein C-III | -0.4 mg/dL | Standard Error 0.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Apolipoprotein C-III | -0.7 mg/dL | Standard Error 0.29 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein C-III | -0.3 mg/dL | Standard Error 0.29 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.0 mg/dL | Standard Error 0.28 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.4 mg/dL | Standard Error 0.29 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein C-III | -0.3 mg/dL | Standard Error 0.29 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.0 mg/dL | Standard Error 0.28 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.3 mg/dL | Standard Error 0.28 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.1 mg/dL | Standard Error 0.29 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.4 mg/dL | Standard Error 0.29 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Apolipoprotein C-III | -1.2 mg/dL | Standard Error 0.29 |
Secondary
Change From Baseline to Week 12 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Body Weight | -0.46 kg | Standard Error 0.216 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Body Weight | -0.14 kg | Standard Error 0.217 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Body Weight | -0.56 kg | Standard Error 0.216 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Body Weight | 0.39 kg | Standard Error 0.217 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Body Weight | 0.22 kg | Standard Error 0.213 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Body Weight | 0.39 kg | Standard Error 0.215 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Body Weight | 0.75 kg | Standard Error 0.217 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Body Weight | 0.60 kg | Standard Error 0.215 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Body Weight | 0.98 kg | Standard Error 0.216 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Body Weight | 0.55 kg | Standard Error 0.216 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Body Weight | 0.88 kg | Standard Error 0.217 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Body Weight | 1.08 kg | Standard Error 0.214 |
Secondary
Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | -3.027 percentage beta cell function | Standard Error 6.4915 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 16.304 percentage beta cell function | Standard Error 6.5165 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 22.996 percentage beta cell function | Standard Error 6.3854 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 2.565 percentage beta cell function | Standard Error 6.4614 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 30.346 percentage beta cell function | Standard Error 6.5157 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 19.887 percentage beta cell function | Standard Error 6.4916 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 1.118 percentage beta cell function | Standard Error 6.603 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 21.045 percentage beta cell function | Standard Error 6.6358 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 19.935 percentage beta cell function | Standard Error 6.5444 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 4.023 percentage beta cell function | Standard Error 6.624 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 19.938 percentage beta cell function | Standard Error 6.6025 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function | 18.541 percentage beta cell function | Standard Error 6.5456 |
Secondary
Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | 0.337 insulin resistance | Standard Error 0.5333 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | 0.063 insulin resistance | Standard Error 0.5375 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | 0.041 insulin resistance | Standard Error 0.527 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -1.012 insulin resistance | Standard Error 0.533 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -1.819 insulin resistance | Standard Error 0.5376 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.305 insulin resistance | Standard Error 0.5352 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.278 insulin resistance | Standard Error 0.5446 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -1.457 insulin resistance | Standard Error 0.5473 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.665 insulin resistance | Standard Error 0.54 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.202 insulin resistance | Standard Error 0.5447 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.615 insulin resistance | Standard Error 0.5446 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance | -2.742 insulin resistance | Standard Error 0.5377 |
Secondary
Change From Baseline to Week 12 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in C-peptide Levels | -0.055 ng/mL | Standard Error 0.1338 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in C-peptide Levels | 0.083 ng/mL | Standard Error 0.136 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in C-peptide Levels | 0.140 ng/mL | Standard Error 0.1349 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in C-peptide Levels | 0.116 ng/mL | Standard Error 0.1344 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in C-peptide Levels | -0.155 ng/mL | Standard Error 0.1344 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in C-peptide Levels | -0.215 ng/mL | Standard Error 0.1338 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in C-peptide Levels | -0.439 ng/mL | Standard Error 0.1372 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in C-peptide Levels | -0.212 ng/mL | Standard Error 0.1345 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in C-peptide Levels | -0.326 ng/mL | Standard Error 0.1343 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in C-peptide Levels | -0.483 ng/mL | Standard Error 0.1344 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in C-peptide Levels | -0.381 ng/mL | Standard Error 0.136 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in C-peptide Levels | -0.464 ng/mL | Standard Error 0.1339 |
Secondary
Change From Baseline to Week 12 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Fasting Plasma Glucose | 3.4 mg/dL | Standard Error 3.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Fasting Plasma Glucose | -19.3 mg/dL | Standard Error 3.25 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Fasting Plasma Glucose | -23.3 mg/dL | Standard Error 3.19 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -23.0 mg/dL | Standard Error 3.18 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -42.9 mg/dL | Standard Error 3.16 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -42.5 mg/dL | Standard Error 3.14 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -26.6 mg/dL | Standard Error 3.21 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -42.8 mg/dL | Standard Error 3.16 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -49.0 mg/dL | Standard Error 3.19 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -41.3 mg/dL | Standard Error 3.16 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -49.2 mg/dL | Standard Error 3.17 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Plasma Glucose | -51.4 mg/dL | Standard Error 3.18 |
Secondary
Change From Baseline to Week 12 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Fasting Proinsulin | -1.0 pmol/L | Standard Error 1.56 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Fasting Proinsulin | -0.7 pmol/L | Standard Error 1.57 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Fasting Proinsulin | -2.3 pmol/L | Standard Error 1.56 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Proinsulin | -5.3 pmol/L | Standard Error 1.57 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Proinsulin | -10.1 pmol/L | Standard Error 1.58 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Fasting Proinsulin | -8.8 pmol/L | Standard Error 1.58 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Proinsulin | -11.2 pmol/L | Standard Error 1.6 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Proinsulin | -12.1 pmol/L | Standard Error 1.63 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Fasting Proinsulin | -12.7 pmol/L | Standard Error 1.58 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Proinsulin | -8.1 pmol/L | Standard Error 1.58 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Proinsulin | -12.7 pmol/L | Standard Error 1.61 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Fasting Proinsulin | -13.2 pmol/L | Standard Error 1.58 |
Secondary
Change From Baseline to Week 12 in Free Fatty Acids
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Free Fatty Acids | 0.0067 mmol/L | Standard Error 0.02493 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Free Fatty Acids | -0.0149 mmol/L | Standard Error 0.02535 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Free Fatty Acids | -0.0769 mmol/L | Standard Error 0.02535 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Free Fatty Acids | -0.0879 mmol/L | Standard Error 0.02547 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1305 mmol/L | Standard Error 0.02502 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1291 mmol/L | Standard Error 0.02512 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Free Fatty Acids | -0.0395 mmol/L | Standard Error 0.02592 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1167 mmol/L | Standard Error 0.02515 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1126 mmol/L | Standard Error 0.02534 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Free Fatty Acids | -0.0848 mmol/L | Standard Error 0.02567 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1447 mmol/L | Standard Error 0.02503 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Free Fatty Acids | -0.1401 mmol/L | Standard Error 0.02514 |
Secondary
Change From Baseline to Week 12 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in HbA1c | -0.28 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in HbA1c | -0.84 percentage of glycosylated hemoglobin | Standard Error 0.069 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in HbA1c | -0.92 percentage of glycosylated hemoglobin | Standard Error 0.068 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in HbA1c | -0.65 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in HbA1c | -1.24 percentage of glycosylated hemoglobin | Standard Error 0.066 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in HbA1c | -1.26 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in HbA1c | -0.77 percentage of glycosylated hemoglobin | Standard Error 0.068 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in HbA1c | -1.29 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in HbA1c | -1.33 percentage of glycosylated hemoglobin | Standard Error 0.068 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in HbA1c | -1.02 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in HbA1c | -1.34 percentage of glycosylated hemoglobin | Standard Error 0.067 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in HbA1c | -1.53 percentage of glycosylated hemoglobin | Standard Error 0.067 |
Secondary
Change From Baseline to Week 12 in HDL Particles
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 0.17 μmol/L | Standard Error 0.325 |
| Pioglitazone Alone | Change From Baseline to Week 12 in HDL Particles | Large Particles | -0.21 μmol/L | Standard Error 0.185 |
| Pioglitazone Alone | Change From Baseline to Week 12 in HDL Particles | Small Particles | -0.07 μmol/L | Standard Error 0.435 |
| Pioglitazone Alone | Change From Baseline to Week 12 in HDL Particles | Total Particles | -0.08 μmol/L | Standard Error 0.368 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Large Particles | -0.29 μmol/L | Standard Error 0.19 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Total Particles | -0.06 μmol/L | Standard Error 0.377 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Medium Particles | -0.24 μmol/L | Standard Error 0.333 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Small Particles | 0.43 μmol/L | Standard Error 0.447 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.16 μmol/L | Standard Error 0.375 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Large Particles | -0.10 μmol/L | Standard Error 0.189 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Medium Particles | -0.01 μmol/L | Standard Error 0.332 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in HDL Particles | Small Particles | 0.27 μmol/L | Standard Error 0.445 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.90 μmol/L | Standard Error 0.377 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -0.25 μmol/L | Standard Error 0.446 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 0.53 μmol/L | Standard Error 0.19 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 0.81 μmol/L | Standard Error 0.334 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 0.24 μmol/L | Standard Error 0.189 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -1.09 μmol/L | Standard Error 0.445 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 1.15 μmol/L | Standard Error 0.332 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.37 μmol/L | Standard Error 0.375 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.55 μmol/L | Standard Error 0.37 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 0.50 μmol/L | Standard Error 0.186 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -0.63 μmol/L | Standard Error 0.439 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 0.65 μmol/L | Standard Error 0.328 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 1.21 μmol/L | Standard Error 0.338 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 1.29 μmol/L | Standard Error 0.382 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 1.09 μmol/L | Standard Error 0.192 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -0.92 μmol/L | Standard Error 0.453 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 0.95 μmol/L | Standard Error 0.19 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.75 μmol/L | Standard Error 0.377 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -1.18 μmol/L | Standard Error 0.447 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 0.97 μmol/L | Standard Error 0.334 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 1.89 μmol/L | Standard Error 0.338 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -2.82 μmol/L | Standard Error 0.452 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 1.12 μmol/L | Standard Error 0.192 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.15 μmol/L | Standard Error 0.382 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.40 μmol/L | Standard Error 0.384 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 2.06 μmol/L | Standard Error 0.339 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 1.06 μmol/L | Standard Error 0.193 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -2.82 μmol/L | Standard Error 0.455 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 1.17 μmol/L | Standard Error 0.186 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 1.30 μmol/L | Standard Error 0.326 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.63 μmol/L | Standard Error 0.369 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -1.84 μmol/L | Standard Error 0.437 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Total Particles | 0.60 μmol/L | Standard Error 0.372 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Medium Particles | 2.31 μmol/L | Standard Error 0.329 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Large Particles | 1.06 μmol/L | Standard Error 0.187 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in HDL Particles | Small Particles | -2.84 μmol/L | Standard Error 0.441 |
Secondary
Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | -0.2 mg/dL | Standard Error 0.64 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 0.0 mg/dL | Standard Error 0.65 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 0.3 mg/dL | Standard Error 0.64 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 3.8 mg/dL | Standard Error 0.64 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 3.7 mg/dL | Standard Error 0.63 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 3.7 mg/dL | Standard Error 0.63 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 6.3 mg/dL | Standard Error 0.64 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 5.8 mg/dL | Standard Error 0.63 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 5.3 mg/dL | Standard Error 0.64 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 0.63 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 6.3 mg/dL | Standard Error 0.64 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol | 6.4 mg/dL | Standard Error 0.64 |
Secondary
Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -1.1053 mg/L | Standard Error 0.55528 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -1.0730 mg/L | Standard Error 0.56942 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | 0.3516 mg/L | Standard Error 0.55954 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -0.9166 mg/L | Standard Error 0.56902 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.2362 mg/L | Standard Error 0.55706 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.4217 mg/L | Standard Error 0.55929 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.7023 mg/L | Standard Error 0.55971 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.2143 mg/L | Standard Error 0.55757 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -1.0006 mg/L | Standard Error 0.56412 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.4212 mg/L | Standard Error 0.57137 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.9032 mg/L | Standard Error 0.55979 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein | -2.2978 mg/L | Standard Error 0.55243 |
Secondary
Change From Baseline to Week 12 in IDL Particles
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in IDL Particles | 1.6 nmol/L | Standard Error 3.6 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in IDL Particles | -11.1 nmol/L | Standard Error 3.7 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in IDL Particles | -6.0 nmol/L | Standard Error 3.68 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in IDL Particles | 5.1 nmol/L | Standard Error 3.7 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in IDL Particles | -6.0 nmol/L | Standard Error 3.68 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in IDL Particles | -2.3 nmol/L | Standard Error 3.64 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in IDL Particles | -2.2 nmol/L | Standard Error 3.75 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in IDL Particles | -6.3 nmol/L | Standard Error 3.7 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in IDL Particles | -8.1 nmol/L | Standard Error 3.75 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in IDL Particles | -1.5 nmol/L | Standard Error 3.76 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in IDL Particles | 0.7 nmol/L | Standard Error 3.62 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in IDL Particles | -6.5 nmol/L | Standard Error 3.65 |
Secondary
Change From Baseline to Week 12 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Insulin Levels | 0.06 µIU/mL | Standard Error 0.849 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Insulin Levels | 1.79 µIU/mL | Standard Error 0.859 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Insulin Levels | 1.93 µIU/mL | Standard Error 0.846 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Insulin Levels | -1.29 µIU/mL | Standard Error 0.852 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Insulin Levels | -1.47 µIU/mL | Standard Error 0.859 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Insulin Levels | -2.01 µIU/mL | Standard Error 0.859 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Insulin Levels | -3.61 µIU/mL | Standard Error 0.87 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Insulin Levels | -1.36 µIU/mL | Standard Error 0.882 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Insulin Levels | -2.83 µIU/mL | Standard Error 0.863 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Insulin Levels | -2.95 µIU/mL | Standard Error 0.863 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Insulin Levels | -2.35 µIU/mL | Standard Error 0.874 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Insulin Levels | -3.01 µIU/mL | Standard Error 0.859 |
Secondary
Change From Baseline to Week 12 in LDL Particles
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in LDL Particles | Large Particles | 4.7 nmol/L | Standard Error 16.74 |
| Pioglitazone Alone | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | 36.4 nmol/L | Standard Error 27.65 |
| Pioglitazone Alone | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | 9.4 nmol/L | Standard Error 6.87 |
| Pioglitazone Alone | Change From Baseline to Week 12 in LDL Particles | Total Particles | 52.0 nmol/L | Standard Error 29.17 |
| Pioglitazone Alone | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | 45.1 nmol/L | Standard Error 33.98 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Total Particles | -39.1 nmol/L | Standard Error 29.92 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -44.1 nmol/L | Standard Error 28.34 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Large Particles | 21.1 nmol/L | Standard Error 17.16 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -52.0 nmol/L | Standard Error 34.83 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -7.7 nmol/L | Standard Error 7.04 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Large Particles | -8.0 nmol/L | Standard Error 17.09 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Total Particles | -69.9 nmol/L | Standard Error 29.8 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -51.9 nmol/L | Standard Error 28.23 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -56.5 nmol/L | Standard Error 34.7 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -5.1 nmol/L | Standard Error 7.02 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -48.8 nmol/L | Standard Error 29.91 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 56.2 nmol/L | Standard Error 17.15 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -109.9 nmol/L | Standard Error 34.83 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -89.2 nmol/L | Standard Error 28.33 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -20.3 nmol/L | Standard Error 7.04 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -170.3 nmol/L | Standard Error 28.22 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 73.8 nmol/L | Standard Error 17.08 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -211.0 nmol/L | Standard Error 34.69 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -41.1 nmol/L | Standard Error 7.01 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -143.5 nmol/L | Standard Error 29.79 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -256.3 nmol/L | Standard Error 34.26 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -48.0 nmol/L | Standard Error 6.93 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -175.6 nmol/L | Standard Error 29.43 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 85.7 nmol/L | Standard Error 16.86 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -207.6 nmol/L | Standard Error 27.87 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -96.2 nmol/L | Standard Error 30.37 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 83.9 nmol/L | Standard Error 17.43 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -34.4 nmol/L | Standard Error 7.14 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -184.1 nmol/L | Standard Error 35.32 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -149.8 nmol/L | Standard Error 28.74 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -58.2 nmol/L | Standard Error 7.05 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 126.2 nmol/L | Standard Error 17.18 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -195.8 nmol/L | Standard Error 29.93 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -313.7 nmol/L | Standard Error 34.85 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -255.7 nmol/L | Standard Error 28.36 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -345.4 nmol/L | Standard Error 35.29 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -248.8 nmol/L | Standard Error 30.31 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -64.1 nmol/L | Standard Error 7.14 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 105.7 nmol/L | Standard Error 17.39 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -281.5 nmol/L | Standard Error 28.72 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -280.4 nmol/L | Standard Error 35.46 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -225.0 nmol/L | Standard Error 28.85 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -55.4 nmol/L | Standard Error 7.17 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 116.9 nmol/L | Standard Error 17.48 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -167.0 nmol/L | Standard Error 30.46 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 135.2 nmol/L | Standard Error 16.79 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -337.9 nmol/L | Standard Error 34.08 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -271.0 nmol/L | Standard Error 27.73 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -66.8 nmol/L | Standard Error 6.89 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -202.2 nmol/L | Standard Error 29.27 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Small Particles | -392.7 nmol/L | Standard Error 34.38 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Large Particles | 116.1 nmol/L | Standard Error 16.95 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Medium-Small Particles | -68.2 nmol/L | Standard Error 6.96 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Total Particles | -285.8 nmol/L | Standard Error 29.52 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in LDL Particles | Very Small Particles | -325.0 nmol/L | Standard Error 27.97 |
Secondary
Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 6.5 mg/dL | Standard Error 2.26 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 1.9 mg/dL | Standard Error 2.3 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 3.7 mg/dL | Standard Error 2.26 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 8.9 mg/dL | Standard Error 2.24 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 3.3 mg/dL | Standard Error 2.21 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 3.8 mg/dL | Standard Error 2.24 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 2.26 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 1.9 mg/dL | Standard Error 2.23 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 0.9 mg/dL | Standard Error 2.25 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 5.7 mg/dL | Standard Error 2.23 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | 4.9 mg/dL | Standard Error 2.26 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol | -0.3 mg/dL | Standard Error 2.22 |
Secondary
Change From Baseline to Week 12 in Mean HDL Particle Size
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.00 nm | Standard Error 0.023 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.00 nm | Standard Error 0.023 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.00 nm | Standard Error 0.023 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.06 nm | Standard Error 0.023 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.07 nm | Standard Error 0.023 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.09 nm | Standard Error 0.023 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.10 nm | Standard Error 0.023 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.15 nm | Standard Error 0.023 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.17 nm | Standard Error 0.023 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.18 nm | Standard Error 0.024 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.17 nm | Standard Error 0.023 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean HDL Particle Size | 0.21 nm | Standard Error 0.023 |
Secondary
Change From Baseline to Week 12 in Mean LDL Particle Size
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Mean LDL Particle Size | -0.05 nm | Standard Error 0.057 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.13 nm | Standard Error 0.059 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.06 nm | Standard Error 0.059 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.25 nm | Standard Error 0.059 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.43 nm | Standard Error 0.059 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.49 nm | Standard Error 0.058 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.44 nm | Standard Error 0.06 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.61 nm | Standard Error 0.059 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.61 nm | Standard Error 0.06 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.58 nm | Standard Error 0.06 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.68 nm | Standard Error 0.058 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean LDL Particle Size | 0.73 nm | Standard Error 0.058 |
Secondary
Change From Baseline to Week 12 in Mean VLDL Particle Size
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Mean VLDL Particle Size | 0.65 nm | Standard Error 0.664 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Mean VLDL Particle Size | 0.12 nm | Standard Error 0.681 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Mean VLDL Particle Size | -0.18 nm | Standard Error 0.678 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.81 nm | Standard Error 0.681 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.10 nm | Standard Error 0.681 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.56 nm | Standard Error 0.669 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -3.16 nm | Standard Error 0.69 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.88 nm | Standard Error 0.681 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.49 nm | Standard Error 0.69 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -2.37 nm | Standard Error 0.694 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -4.00 nm | Standard Error 0.666 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Mean VLDL Particle Size | -4.03 nm | Standard Error 0.672 |
Secondary
Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | 20.6 mg/dL | Standard Error 6.56 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -4.9 mg/dL | Standard Error 6.73 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -7.8 mg/dL | Standard Error 6.7 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -12.9 mg/dL | Standard Error 6.72 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -21.8 mg/dL | Standard Error 6.7 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -27.2 mg/dL | Standard Error 6.61 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -18.3 mg/dL | Standard Error 6.82 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -29.8 mg/dL | Standard Error 6.73 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -31.6 mg/dL | Standard Error 6.82 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -27.9 mg/dL | Standard Error 6.85 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -35.1 mg/dL | Standard Error 6.59 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides | -36.0 mg/dL | Standard Error 6.64 |
Secondary
Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -4.55 ng/mL | Standard Error 3.367 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | 3.54 ng/mL | Standard Error 3.35 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -1.80 ng/mL | Standard Error 3.353 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -5.32 ng/mL | Standard Error 3.34 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -6.28 ng/mL | Standard Error 3.26 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -10.94 ng/mL | Standard Error 3.32 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -8.53 ng/mL | Standard Error 3.353 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -10.47 ng/mL | Standard Error 3.336 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -1.71 ng/mL | Standard Error 3.321 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | 1.85 ng/mL | Standard Error 3.539 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -9.13 ng/mL | Standard Error 3.277 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 | -12.63 ng/mL | Standard Error 3.306 |
Secondary
Change From Baseline to Week 12 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.006 ratio | Standard Error 0.0142 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.024 ratio | Standard Error 0.0144 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.041 ratio | Standard Error 0.0141 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.041 ratio | Standard Error 0.0142 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.073 ratio | Standard Error 0.0144 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.056 ratio | Standard Error 0.0144 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.063 ratio | Standard Error 0.0146 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.072 ratio | Standard Error 0.0149 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.088 ratio | Standard Error 0.0144 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.021 ratio | Standard Error 0.0144 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.112 ratio | Standard Error 0.0146 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Proinsulin/Insulin Ratio | -0.101 ratio | Standard Error 0.0144 |
Secondary
Change From Baseline to Week 12 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Total Cholesterol Levels | 7.8 mg/dL | Standard Error 2.54 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Total Cholesterol Levels | 0.4 mg/dL | Standard Error 2.57 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Total Cholesterol Levels | 0.1 mg/dL | Standard Error 2.56 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Total Cholesterol Levels | 8.7 mg/dL | Standard Error 2.54 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Total Cholesterol Levels | 1.9 mg/dL | Standard Error 2.51 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Total Cholesterol Levels | -0.2 mg/dL | Standard Error 2.52 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Total Cholesterol Levels | 7.3 mg/dL | Standard Error 2.56 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Total Cholesterol Levels | 0.3 mg/dL | Standard Error 2.52 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Total Cholesterol Levels | -1.0 mg/dL | Standard Error 2.55 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Total Cholesterol Levels | 3.7 mg/dL | Standard Error 2.53 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Total Cholesterol Levels | 1.7 mg/dL | Standard Error 2.54 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Total Cholesterol Levels | -3.9 mg/dL | Standard Error 2.54 |
Secondary
Change From Baseline to Week 12 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in Triglyceride Levels | 18.9 mg/dL | Standard Error 7.35 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in Triglyceride Levels | -4.3 mg/dL | Standard Error 7.44 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in Triglyceride Levels | -18.1 mg/dL | Standard Error 7.41 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in Triglyceride Levels | -24.1 mg/dL | Standard Error 7.34 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in Triglyceride Levels | -37.4 mg/dL | Standard Error 7.26 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in Triglyceride Levels | -44.0 mg/dL | Standard Error 7.29 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in Triglyceride Levels | -37.4 mg/dL | Standard Error 7.4 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in Triglyceride Levels | -47.9 mg/dL | Standard Error 7.29 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in Triglyceride Levels | -46.8 mg/dL | Standard Error 7.38 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in Triglyceride Levels | -42.1 mg/dL | Standard Error 7.31 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in Triglyceride Levels | -57.1 mg/dL | Standard Error 7.35 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in Triglyceride Levels | -57.4 mg/dL | Standard Error 7.35 |
Secondary
Change From Baseline to Week 12 in VLDL / Chylomicron Particles
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | 5.82 nmol/L | Standard Error 3.013 |
| Pioglitazone Alone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | 1.12 nmol/L | Standard Error 0.482 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -1.59 nmol/L | Standard Error 3.092 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -0.42 nmol/L | Standard Error 0.495 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -5.32 nmol/L | Standard Error 3.077 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -0.27 nmol/L | Standard Error 0.493 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | 2.52 nmol/L | Standard Error 3.089 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -1.20 nmol/L | Standard Error 0.495 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -1.63 nmol/L | Standard Error 0.493 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -3.46 nmol/L | Standard Error 3.077 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -5.57 nmol/L | Standard Error 3.037 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -1.81 nmol/L | Standard Error 0.486 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -1.69 nmol/L | Standard Error 0.502 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | 0.45 nmol/L | Standard Error 3.135 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -7.82 nmol/L | Standard Error 3.092 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -2.19 nmol/L | Standard Error 0.495 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -6.54 nmol/L | Standard Error 3.132 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -2.29 nmol/L | Standard Error 0.501 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -8.58 nmol/L | Standard Error 3.147 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -1.97 nmol/L | Standard Error 0.504 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -2.81 nmol/L | Standard Error 0.484 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -7.99 nmol/L | Standard Error 3.027 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Large Particles | -2.45 nmol/L | Standard Error 0.489 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Particles | Total Particles | -9.76 nmol/L | Standard Error 3.051 |
Secondary
Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | 19.9 mg/dL | Standard Error 6.51 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -3.5 mg/dL | Standard Error 6.69 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -6.4 mg/dL | Standard Error 6.65 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -14.2 mg/dL | Standard Error 6.68 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -21.1 mg/dL | Standard Error 6.65 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -26.5 mg/dL | Standard Error 6.56 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -19.1 mg/dL | Standard Error 6.78 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -29.5 mg/dL | Standard Error 6.69 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -30.1 mg/dL | Standard Error 6.77 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -28.4 mg/dL | Standard Error 6.8 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -35.5 mg/dL | Standard Error 6.55 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides | -34.8 mg/dL | Standard Error 6.6 |
Secondary
Change From Baseline to Week 12 in VLDL Particles
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Time frame: Baseline and Week 12
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | 2.13 nmol/L | Standard Error 1.962 |
| Pioglitazone Alone | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 2.76 nmol/L | Standard Error 1.758 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -1.13 nmol/L | Standard Error 2.014 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 0.39 nmol/L | Standard Error 1.804 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -2.88 nmol/L | Standard Error 2.003 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 12 in VLDL Particles | Small Particles | -2.30 nmol/L | Standard Error 1.797 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -2.25 nmol/L | Standard Error 2.011 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 5.99 nmol/L | Standard Error 1.803 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 1.16 nmol/L | Standard Error 1.796 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -3.16 nmol/L | Standard Error 2.004 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -6.51 nmol/L | Standard Error 1.977 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 2.60 nmol/L | Standard Error 1.772 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 4.39 nmol/L | Standard Error 1.829 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -2.59 nmol/L | Standard Error 2.041 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -6.70 nmol/L | Standard Error 2.013 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 1.15 nmol/L | Standard Error 1.806 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -7.05 nmol/L | Standard Error 2.039 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 2.51 nmol/L | Standard Error 1.828 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -8.64 nmol/L | Standard Error 2.048 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 2.22 nmol/L | Standard Error 1.839 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 1.80 nmol/L | Standard Error 1.765 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -6.38 nmol/L | Standard Error 1.971 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Small Particles | 0.73 nmol/L | Standard Error 1.78 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 12 in VLDL Particles | Medium Particles | -8.50 nmol/L | Standard Error 1.987 |
Secondary
Change From Baseline to Week 16 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in C-peptide Levels | -0.076 ng/mL | Standard Error 0.0783 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in C-peptide Levels | 0.032 ng/mL | Standard Error 0.0796 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in C-peptide Levels | 0.101 ng/mL | Standard Error 0.0789 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in C-peptide Levels | -0.242 ng/mL | Standard Error 0.0786 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in C-peptide Levels | -0.282 ng/mL | Standard Error 0.078 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in C-peptide Levels | -0.184 ng/mL | Standard Error 0.0783 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in C-peptide Levels | -0.410 ng/mL | Standard Error 0.0796 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in C-peptide Levels | -0.318 ng/mL | Standard Error 0.0783 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in C-peptide Levels | -0.306 ng/mL | Standard Error 0.0786 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in C-peptide Levels | -0.404 ng/mL | Standard Error 0.0786 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in C-peptide Levels | -0.431 ng/mL | Standard Error 0.0789 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in C-peptide Levels | -0.510 ng/mL | Standard Error 0.0783 |
Secondary
Change From Baseline to Week 16 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Fasting Plasma Glucose | 1.4 mg/dL | Standard Error 3.2 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Fasting Plasma Glucose | -16.2 mg/dL | Standard Error 3.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Fasting Plasma Glucose | -22.6 mg/dL | Standard Error 3.24 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -21.2 mg/dL | Standard Error 3.22 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -41.6 mg/dL | Standard Error 3.2 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -39.1 mg/dL | Standard Error 3.19 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -26.3 mg/dL | Standard Error 3.25 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -41.5 mg/dL | Standard Error 3.2 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -43.4 mg/dL | Standard Error 3.24 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -36.3 mg/dL | Standard Error 3.2 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -47.9 mg/dL | Standard Error 3.21 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Plasma Glucose | -53.8 mg/dL | Standard Error 3.22 |
Secondary
Change From Baseline to Week 16 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Fasting Proinsulin | -3.0 pmol/L | Standard Error 1.58 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Fasting Proinsulin | 0.0 pmol/L | Standard Error 1.6 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Fasting Proinsulin | -2.3 pmol/L | Standard Error 1.58 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Proinsulin | -3.7 pmol/L | Standard Error 1.59 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Proinsulin | -11.0 pmol/L | Standard Error 1.6 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Fasting Proinsulin | -8.4 pmol/L | Standard Error 1.6 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Proinsulin | -10.0 pmol/L | Standard Error 1.62 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Proinsulin | -12.6 pmol/L | Standard Error 1.65 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Fasting Proinsulin | -11.2 pmol/L | Standard Error 1.6 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Proinsulin | -8.0 pmol/L | Standard Error 1.6 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Proinsulin | -13.0 pmol/L | Standard Error 1.63 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Fasting Proinsulin | -14.4 pmol/L | Standard Error 1.6 |
Secondary
Change From Baseline to Week 16 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in HbA1c | -0.27 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in HbA1c | -0.82 percentage of glycosylated hemoglobin | Standard Error 0.072 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in HbA1c | -1.03 percentage of glycosylated hemoglobin | Standard Error 0.072 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in HbA1c | -0.74 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in HbA1c | -1.36 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in HbA1c | -1.36 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in HbA1c | -0.91 percentage of glycosylated hemoglobin | Standard Error 0.072 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in HbA1c | -1.42 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in HbA1c | -1.45 percentage of glycosylated hemoglobin | Standard Error 0.072 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in HbA1c | -1.12 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in HbA1c | -1.53 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in HbA1c | -1.66 percentage of glycosylated hemoglobin | Standard Error 0.071 |
Secondary
Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | -0.3 mg/dL | Standard Error 0.67 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 0.4 mg/dL | Standard Error 0.68 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 0.7 mg/dL | Standard Error 0.67 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 3.9 mg/dL | Standard Error 0.67 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 4.2 mg/dL | Standard Error 0.66 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 4.0 mg/dL | Standard Error 0.66 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 5.7 mg/dL | Standard Error 0.67 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 5.5 mg/dL | Standard Error 0.66 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 4.3 mg/dL | Standard Error 0.67 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 5.9 mg/dL | Standard Error 0.66 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 0.67 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol | 6.7 mg/dL | Standard Error 0.67 |
Secondary
Change From Baseline to Week 16 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Insulin Levels | 0.34 µIU/mL | Standard Error 0.833 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Insulin Levels | 1.22 µIU/mL | Standard Error 0.843 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Insulin Levels | 1.83 µIU/mL | Standard Error 0.83 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Insulin Levels | -0.63 µIU/mL | Standard Error 0.836 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Insulin Levels | -2.28 µIU/mL | Standard Error 0.84 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Insulin Levels | -1.11 µIU/mL | Standard Error 0.843 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Insulin Levels | -3.46 µIU/mL | Standard Error 0.851 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Insulin Levels | -2.50 µIU/mL | Standard Error 0.866 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Insulin Levels | -2.82 µIU/mL | Standard Error 0.847 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Insulin Levels | -2.48 µIU/mL | Standard Error 0.847 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Insulin Levels | -3.00 µIU/mL | Standard Error 0.858 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Insulin Levels | -3.52 µIU/mL | Standard Error 0.844 |
Secondary
Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 4.2 mg/dL | Standard Error 2.25 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 1.3 mg/dL | Standard Error 2.29 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 0.9 mg/dL | Standard Error 2.26 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 7.1 mg/dL | Standard Error 2.23 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 2.9 mg/dL | Standard Error 2.21 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 4.6 mg/dL | Standard Error 2.23 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 7.1 mg/dL | Standard Error 2.25 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 2.1 mg/dL | Standard Error 2.23 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 0.8 mg/dL | Standard Error 2.25 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 4.1 mg/dL | Standard Error 2.22 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 4.9 mg/dL | Standard Error 2.25 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol | 1.8 mg/dL | Standard Error 2.21 |
Secondary
Change From Baseline to Week 16 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.026 ratio | Standard Error 0.0132 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.036 ratio | Standard Error 0.0133 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.046 ratio | Standard Error 0.0131 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.035 ratio | Standard Error 0.0132 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.078 ratio | Standard Error 0.0133 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.066 ratio | Standard Error 0.0134 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.035 ratio | Standard Error 0.0135 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.094 ratio | Standard Error 0.0138 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.061 ratio | Standard Error 0.0134 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.030 ratio | Standard Error 0.0134 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.102 ratio | Standard Error 0.0136 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Proinsulin/Insulin Ratio | -0.104 ratio | Standard Error 0.0133 |
Secondary
Change From Baseline to Week 16 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Total Cholesterol Levels | 5.0 mg/dL | Standard Error 2.62 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Total Cholesterol Levels | -0.5 mg/dL | Standard Error 2.66 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Total Cholesterol Levels | -2.9 mg/dL | Standard Error 2.65 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Total Cholesterol Levels | 7.2 mg/dL | Standard Error 2.62 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Total Cholesterol Levels | -0.4 mg/dL | Standard Error 2.59 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Total Cholesterol Levels | 3.2 mg/dL | Standard Error 2.6 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Total Cholesterol Levels | 10.0 mg/dL | Standard Error 2.65 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Total Cholesterol Levels | 0.9 mg/dL | Standard Error 2.61 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Total Cholesterol Levels | -1.2 mg/dL | Standard Error 2.63 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Total Cholesterol Levels | 2.3 mg/dL | Standard Error 2.61 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Total Cholesterol Levels | 2.9 mg/dL | Standard Error 2.62 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Total Cholesterol Levels | -1.8 mg/dL | Standard Error 2.62 |
Secondary
Change From Baseline to Week 16 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 16
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 16 in Triglyceride Levels | 10.6 mg/dL | Standard Error 7.66 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 16 in Triglyceride Levels | -7.5 mg/dL | Standard Error 7.75 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 16 in Triglyceride Levels | -26.8 mg/dL | Standard Error 7.72 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 16 in Triglyceride Levels | -10.5 mg/dL | Standard Error 7.66 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 16 in Triglyceride Levels | -53.0 mg/dL | Standard Error 7.57 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 16 in Triglyceride Levels | -33.8 mg/dL | Standard Error 7.6 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 16 in Triglyceride Levels | -28.2 mg/dL | Standard Error 7.72 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 16 in Triglyceride Levels | -44.2 mg/dL | Standard Error 7.6 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 16 in Triglyceride Levels | -45.9 mg/dL | Standard Error 7.69 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 16 in Triglyceride Levels | -49.4 mg/dL | Standard Error 7.63 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 16 in Triglyceride Levels | -50.7 mg/dL | Standard Error 7.66 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 16 in Triglyceride Levels | -59.1 mg/dL | Standard Error 7.66 |
Secondary
Change From Baseline to Week 1 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 1
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 1 in Fasting Plasma Glucose | 1.8 mg/dL | Standard Error 2.67 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 1 in Fasting Plasma Glucose | -14.5 mg/dL | Standard Error 2.77 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 1 in Fasting Plasma Glucose | -18.6 mg/dL | Standard Error 2.73 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -6.1 mg/dL | Standard Error 2.7 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -21.3 mg/dL | Standard Error 2.69 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -20.9 mg/dL | Standard Error 2.66 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 1 in Fasting Plasma Glucose | 0.4 mg/dL | Standard Error 2.73 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -23.2 mg/dL | Standard Error 2.71 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -23.2 mg/dL | Standard Error 2.72 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -6.7 mg/dL | Standard Error 2.69 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -23.2 mg/dL | Standard Error 2.76 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 1 in Fasting Plasma Glucose | -25.0 mg/dL | Standard Error 2.78 |
Secondary
Change From Baseline to Week 20 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Body Weight | -0.55 kg | Standard Error 0.263 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Body Weight | -0.08 kg | Standard Error 0.264 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Body Weight | -0.48 kg | Standard Error 0.263 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Body Weight | 0.76 kg | Standard Error 0.264 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Body Weight | 0.96 kg | Standard Error 0.259 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Body Weight | 0.85 kg | Standard Error 0.262 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Body Weight | 1.51 kg | Standard Error 0.264 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Body Weight | 1.45 kg | Standard Error 0.261 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Body Weight | 1.76 kg | Standard Error 0.263 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Body Weight | 1.35 kg | Standard Error 0.262 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Body Weight | 1.93 kg | Standard Error 0.264 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Body Weight | 1.76 kg | Standard Error 0.26 |
Secondary
Change From Baseline to Week 20 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in C-peptide Levels | -0.046 ng/mL | Standard Error 0.0799 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in C-peptide Levels | 0.114 ng/mL | Standard Error 0.0812 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in C-peptide Levels | 0.019 ng/mL | Standard Error 0.0805 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in C-peptide Levels | -0.193 ng/mL | Standard Error 0.0802 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in C-peptide Levels | -0.377 ng/mL | Standard Error 0.0792 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in C-peptide Levels | -0.184 ng/mL | Standard Error 0.0795 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in C-peptide Levels | -0.380 ng/mL | Standard Error 0.0812 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in C-peptide Levels | -0.343 ng/mL | Standard Error 0.0799 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in C-peptide Levels | -0.266 ng/mL | Standard Error 0.0802 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in C-peptide Levels | -0.506 ng/mL | Standard Error 0.0802 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in C-peptide Levels | -0.329 ng/mL | Standard Error 0.0805 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in C-peptide Levels | -0.430 ng/mL | Standard Error 0.0799 |
Secondary
Change From Baseline to Week 20 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Fasting Plasma Glucose | 6.7 mg/dL | Standard Error 3.43 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Fasting Plasma Glucose | -8.7 mg/dL | Standard Error 3.53 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Fasting Plasma Glucose | -23.5 mg/dL | Standard Error 3.48 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -22.4 mg/dL | Standard Error 3.46 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -43.0 mg/dL | Standard Error 3.43 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -39.3 mg/dL | Standard Error 3.42 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -26.3 mg/dL | Standard Error 3.49 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -41.1 mg/dL | Standard Error 3.44 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -43.1 mg/dL | Standard Error 3.47 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -35.7 mg/dL | Standard Error 3.43 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -46.8 mg/dL | Standard Error 3.45 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Plasma Glucose | -52.4 mg/dL | Standard Error 3.46 |
Secondary
Change From Baseline to Week 20 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Fasting Proinsulin | -0.9 pmol/L | Standard Error 1.85 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Fasting Proinsulin | 1.5 pmol/L | Standard Error 1.86 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Fasting Proinsulin | -3.0 pmol/L | Standard Error 1.84 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Proinsulin | -3.4 pmol/L | Standard Error 1.86 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Proinsulin | -11.2 pmol/L | Standard Error 1.86 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Fasting Proinsulin | -8.7 pmol/L | Standard Error 1.86 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Proinsulin | -9.3 pmol/L | Standard Error 1.89 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Proinsulin | -10.0 pmol/L | Standard Error 1.92 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Fasting Proinsulin | -10.7 pmol/L | Standard Error 1.87 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Proinsulin | -7.1 pmol/L | Standard Error 1.86 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Proinsulin | -10.2 pmol/L | Standard Error 1.9 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Fasting Proinsulin | -12.5 pmol/L | Standard Error 1.87 |
Secondary
Change From Baseline to Week 20 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in HbA1c | -0.24 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in HbA1c | -0.75 percentage of glycosylated hemoglobin | Standard Error 0.075 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in HbA1c | -0.99 percentage of glycosylated hemoglobin | Standard Error 0.075 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in HbA1c | -0.75 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in HbA1c | -1.39 percentage of glycosylated hemoglobin | Standard Error 0.073 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in HbA1c | -1.37 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in HbA1c | -0.90 percentage of glycosylated hemoglobin | Standard Error 0.075 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in HbA1c | -1.43 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in HbA1c | -1.49 percentage of glycosylated hemoglobin | Standard Error 0.075 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in HbA1c | -1.10 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in HbA1c | -1.57 percentage of glycosylated hemoglobin | Standard Error 0.074 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in HbA1c | -1.66 percentage of glycosylated hemoglobin | Standard Error 0.074 |
Secondary
Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 0.6 mg/dL | Standard Error 0.7 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 0.9 mg/dL | Standard Error 0.71 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 0.5 mg/dL | Standard Error 0.7 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 3.8 mg/dL | Standard Error 0.7 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 4.3 mg/dL | Standard Error 0.69 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 3.9 mg/dL | Standard Error 0.69 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 5.9 mg/dL | Standard Error 0.7 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 5.7 mg/dL | Standard Error 0.69 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 5.3 mg/dL | Standard Error 0.7 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 5.9 mg/dL | Standard Error 0.7 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 7.1 mg/dL | Standard Error 0.7 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol | 6.5 mg/dL | Standard Error 0.7 |
Secondary
Change From Baseline to Week 20 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Insulin Levels | 0.18 µIU/mL | Standard Error 0.873 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Insulin Levels | 2.03 µIU/mL | Standard Error 0.883 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Insulin Levels | 0.76 µIU/mL | Standard Error 0.869 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Insulin Levels | -0.66 µIU/mL | Standard Error 0.876 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Insulin Levels | -2.35 µIU/mL | Standard Error 0.876 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Insulin Levels | -0.90 µIU/mL | Standard Error 0.88 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Insulin Levels | -3.29 µIU/mL | Standard Error 0.891 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Insulin Levels | -2.20 µIU/mL | Standard Error 0.907 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Insulin Levels | -2.29 µIU/mL | Standard Error 0.887 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Insulin Levels | -3.12 µIU/mL | Standard Error 0.887 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Insulin Levels | -1.16 µIU/mL | Standard Error 0.899 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Insulin Levels | -3.01 µIU/mL | Standard Error 0.884 |
Secondary
Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 6.9 mg/dL | Standard Error 2.39 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 2.9 mg/dL | Standard Error 2.43 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 1.9 mg/dL | Standard Error 2.4 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 7.7 mg/dL | Standard Error 2.37 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 4.3 mg/dL | Standard Error 2.34 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 3.0 mg/dL | Standard Error 2.37 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 6.6 mg/dL | Standard Error 2.39 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 2.3 mg/dL | Standard Error 2.36 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 4.1 mg/dL | Standard Error 2.39 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 6.3 mg/dL | Standard Error 2.36 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 2.39 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol | 1.9 mg/dL | Standard Error 2.35 |
Secondary
Change From Baseline to Week 20 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.007 ratio | Standard Error 0.0131 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.014 ratio | Standard Error 0.0132 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.046 ratio | Standard Error 0.013 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.039 ratio | Standard Error 0.0131 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.081 ratio | Standard Error 0.0131 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.065 ratio | Standard Error 0.0132 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.042 ratio | Standard Error 0.0133 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.085 ratio | Standard Error 0.0137 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.077 ratio | Standard Error 0.0133 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.020 ratio | Standard Error 0.0133 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.099 ratio | Standard Error 0.0134 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Proinsulin/Insulin Ratio | -0.092 ratio | Standard Error 0.0132 |
Secondary
Change From Baseline to Week 20 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Total Cholesterol Levels | 6.7 mg/dL | Standard Error 2.7 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Total Cholesterol Levels | 1.8 mg/dL | Standard Error 2.74 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Total Cholesterol Levels | -1.9 mg/dL | Standard Error 2.73 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Total Cholesterol Levels | 6.3 mg/dL | Standard Error 2.7 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Total Cholesterol Levels | 4.0 mg/dL | Standard Error 2.67 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Total Cholesterol Levels | 1.4 mg/dL | Standard Error 2.68 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Total Cholesterol Levels | 7.0 mg/dL | Standard Error 2.73 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Total Cholesterol Levels | 1.1 mg/dL | Standard Error 2.68 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Total Cholesterol Levels | 3.4 mg/dL | Standard Error 2.71 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Total Cholesterol Levels | 4.6 mg/dL | Standard Error 2.69 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Total Cholesterol Levels | 4.0 mg/dL | Standard Error 2.7 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Total Cholesterol Levels | -0.3 mg/dL | Standard Error 2.7 |
Secondary
Change From Baseline to Week 20 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 20
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 20 in Triglyceride Levels | 5.7 mg/dL | Standard Error 7.44 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 20 in Triglyceride Levels | -7.0 mg/dL | Standard Error 7.53 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 20 in Triglyceride Levels | -23.7 mg/dL | Standard Error 7.5 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 20 in Triglyceride Levels | -18.0 mg/dL | Standard Error 7.44 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 20 in Triglyceride Levels | -41.2 mg/dL | Standard Error 7.35 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 20 in Triglyceride Levels | -34.6 mg/dL | Standard Error 7.38 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 20 in Triglyceride Levels | -37.5 mg/dL | Standard Error 7.5 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 20 in Triglyceride Levels | -43.1 mg/dL | Standard Error 7.39 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 20 in Triglyceride Levels | -42.4 mg/dL | Standard Error 7.47 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 20 in Triglyceride Levels | -49.3 mg/dL | Standard Error 7.41 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 20 in Triglyceride Levels | -46.4 mg/dL | Standard Error 7.44 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 20 in Triglyceride Levels | -51.2 mg/dL | Standard Error 7.44 |
Secondary
Change From Baseline to Week 26 in Adiponectin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Adiponectin | 0.43 μg/mL | Standard Error 0.676 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Adiponectin | 0.48 μg/mL | Standard Error 0.681 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Adiponectin | 0.26 μg/mL | Standard Error 0.678 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Adiponectin | 3.30 μg/mL | Standard Error 0.685 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Adiponectin | 4.80 μg/mL | Standard Error 0.664 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Adiponectin | 2.93 μg/mL | Standard Error 0.678 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Adiponectin | 5.90 μg/mL | Standard Error 0.687 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Adiponectin | 6.30 μg/mL | Standard Error 0.676 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Adiponectin | 6.87 μg/mL | Standard Error 0.684 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Adiponectin | 8.75 μg/mL | Standard Error 0.684 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Adiponectin | 8.18 μg/mL | Standard Error 0.678 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Adiponectin | 9.59 μg/mL | Standard Error 0.678 |
Secondary
Change From Baseline to Week 26 in Apolipoprotein A1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Apolipoprotein A1 | -4.9 mg/dL | Standard Error 1.88 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein A1 | -3.0 mg/dL | Standard Error 1.9 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein A1 | -4.2 mg/dL | Standard Error 1.89 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A1 | -3.3 mg/dL | Standard Error 1.9 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A1 | -3.5 mg/dL | Standard Error 1.84 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A1 | -2.9 mg/dL | Standard Error 1.91 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A1 | -0.2 mg/dL | Standard Error 1.89 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A1 | -0.1 mg/dL | Standard Error 1.86 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A1 | -3.2 mg/dL | Standard Error 1.87 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A1 | -1.4 mg/dL | Standard Error 1.89 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A1 | -1.0 mg/dL | Standard Error 1.88 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A1 | -2.2 mg/dL | Standard Error 1.89 |
Secondary
Change From Baseline to Week 26 in Apolipoprotein A2
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Apolipoprotein A2 | 0.1 mg/dL | Standard Error 0.47 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein A2 | 0.2 mg/dL | Standard Error 0.48 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein A2 | 0.4 mg/dL | Standard Error 0.48 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A2 | 1.9 mg/dL | Standard Error 0.48 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A2 | 1.2 mg/dL | Standard Error 0.47 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein A2 | 1.0 mg/dL | Standard Error 0.48 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A2 | 2.7 mg/dL | Standard Error 0.48 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A2 | 2.1 mg/dL | Standard Error 0.47 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein A2 | 1.6 mg/dL | Standard Error 0.47 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A2 | 2.8 mg/dL | Standard Error 0.48 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A2 | 3.1 mg/dL | Standard Error 0.47 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein A2 | 2.7 mg/dL | Standard Error 0.48 |
Secondary
Change From Baseline to Week 26 in Apolipoprotein B
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Apolipoprotein B | 0.6 mg/dL | Standard Error 1.99 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein B | -0.6 mg/dL | Standard Error 2 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein B | -3.7 mg/dL | Standard Error 2 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein B | -1.5 mg/dL | Standard Error 2.01 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein B | -6.0 mg/dL | Standard Error 1.95 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein B | -4.8 mg/dL | Standard Error 2.02 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein B | -3.2 mg/dL | Standard Error 2 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein B | -7.2 mg/dL | Standard Error 1.97 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein B | -8.8 mg/dL | Standard Error 1.98 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein B | -3.6 mg/dL | Standard Error 2 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein B | -6.1 mg/dL | Standard Error 1.99 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein B | -5.5 mg/dL | Standard Error 2 |
Secondary
Change From Baseline to Week 26 in Apolipoprotein C-III
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Apolipoprotein C-III | 0.4 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein C-III | 0.5 mg/dL | Standard Error 0.33 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.7 mg/dL | Standard Error 0.33 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.4 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.6 mg/dL | Standard Error 0.32 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.7 mg/dL | Standard Error 0.33 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein C-III | 0.2 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.4 mg/dL | Standard Error 0.32 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.6 mg/dL | Standard Error 0.32 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein C-III | 0.0 mg/dL | Standard Error 0.33 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.7 mg/dL | Standard Error 0.33 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Apolipoprotein C-III | -0.5 mg/dL | Standard Error 0.33 |
Secondary
Change From Baseline to Week 26 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Body Weight | -0.66 kg | Standard Error 0.291 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Body Weight | -0.02 kg | Standard Error 0.292 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Body Weight | -0.67 kg | Standard Error 0.291 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Body Weight | 0.94 kg | Standard Error 0.292 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Body Weight | 1.25 kg | Standard Error 0.287 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Body Weight | 1.27 kg | Standard Error 0.29 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Body Weight | 1.88 kg | Standard Error 0.292 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Body Weight | 1.89 kg | Standard Error 0.289 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Body Weight | 2.10 kg | Standard Error 0.291 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Body Weight | 1.65 kg | Standard Error 0.29 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Body Weight | 2.30 kg | Standard Error 0.292 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Body Weight | 2.25 kg | Standard Error 0.288 |
Secondary
Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | -0.924 percentage beta cell function | Standard Error 5.226 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 11.812 percentage beta cell function | Standard Error 5.2462 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 17.814 percentage beta cell function | Standard Error 5.1407 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 2.770 percentage beta cell function | Standard Error 5.2018 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 10.977 percentage beta cell function | Standard Error 5.201 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 19.320 percentage beta cell function | Standard Error 5.2044 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 8.983 percentage beta cell function | Standard Error 5.2921 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 22.474 percentage beta cell function | Standard Error 5.3423 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 23.475 percentage beta cell function | Standard Error 5.2687 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 3.427 percentage beta cell function | Standard Error 5.3327 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 21.068 percentage beta cell function | Standard Error 5.3154 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function | 23.752 percentage beta cell function | Standard Error 5.2696 |
Secondary
Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | 0.464 insulin resistance | Standard Error 0.5988 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | 0.311 insulin resistance | Standard Error 0.6036 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -0.179 insulin resistance | Standard Error 0.5918 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -0.864 insulin resistance | Standard Error 0.5985 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -2.300 insulin resistance | Standard Error 0.5986 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -0.223 insulin resistance | Standard Error 0.5985 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -2.061 insulin resistance | Standard Error 0.6089 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -1.871 insulin resistance | Standard Error 0.6147 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -2.056 insulin resistance | Standard Error 0.6064 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -1.789 insulin resistance | Standard Error 0.6117 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -2.456 insulin resistance | Standard Error 0.6116 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance | -2.854 insulin resistance | Standard Error 0.6038 |
Secondary
Change From Baseline to Week 26 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in C-peptide Levels | -0.011 ng/mL | Standard Error 0.0793 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in C-peptide Levels | 0.000 ng/mL | Standard Error 0.0802 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in C-peptide Levels | 0.059 ng/mL | Standard Error 0.0799 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in C-peptide Levels | -0.239 ng/mL | Standard Error 0.0792 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in C-peptide Levels | -0.380 ng/mL | Standard Error 0.0783 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in C-peptide Levels | -0.204 ng/mL | Standard Error 0.0789 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in C-peptide Levels | -0.353 ng/mL | Standard Error 0.0805 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in C-peptide Levels | -0.235 ng/mL | Standard Error 0.079 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in C-peptide Levels | -0.300 ng/mL | Standard Error 0.0795 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in C-peptide Levels | -0.429 ng/mL | Standard Error 0.0793 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in C-peptide Levels | -0.421 ng/mL | Standard Error 0.0796 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in C-peptide Levels | -0.474 ng/mL | Standard Error 0.0793 |
Secondary
Change From Baseline to Week 26 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Fasting Plasma Glucose | 6.5 mg/dL | Standard Error 3.5 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Fasting Plasma Glucose | -13.2 mg/dL | Standard Error 3.59 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Fasting Plasma Glucose | -18.6 mg/dL | Standard Error 3.54 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -23.6 mg/dL | Standard Error 3.52 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -42.0 mg/dL | Standard Error 3.5 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -38.0 mg/dL | Standard Error 3.48 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -28.8 mg/dL | Standard Error 3.55 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -42.2 mg/dL | Standard Error 3.5 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -41.7 mg/dL | Standard Error 3.54 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -32.4 mg/dL | Standard Error 3.49 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -51.3 mg/dL | Standard Error 3.51 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Plasma Glucose | -52.7 mg/dL | Standard Error 3.52 |
Secondary
Change From Baseline to Week 26 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Fasting Proinsulin | 1.2 pmol/L | Standard Error 1.87 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Fasting Proinsulin | 0.7 pmol/L | Standard Error 1.88 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Fasting Proinsulin | -3.3 pmol/L | Standard Error 1.86 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Proinsulin | -3.5 pmol/L | Standard Error 1.88 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Proinsulin | -10.9 pmol/L | Standard Error 1.88 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Fasting Proinsulin | -7.2 pmol/L | Standard Error 1.88 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Proinsulin | -8.4 pmol/L | Standard Error 1.91 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Proinsulin | -8.9 pmol/L | Standard Error 1.95 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Fasting Proinsulin | -8.8 pmol/L | Standard Error 1.89 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Proinsulin | -4.1 pmol/L | Standard Error 1.89 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Proinsulin | -12.1 pmol/L | Standard Error 1.93 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Fasting Proinsulin | -12.6 pmol/L | Standard Error 1.89 |
Secondary
Change From Baseline to Week 26 in Free Fatty Acids
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Free Fatty Acids | -0.0387 mmol/L | Standard Error 0.01788 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Free Fatty Acids | -0.0427 mmol/L | Standard Error 0.01802 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Free Fatty Acids | -0.0386 mmol/L | Standard Error 0.01787 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0561 mmol/L | Standard Error 0.01825 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0752 mmol/L | Standard Error 0.01772 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0972 mmol/L | Standard Error 0.01793 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0737 mmol/L | Standard Error 0.01817 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0956 mmol/L | Standard Error 0.01788 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Free Fatty Acids | -0.1232 mmol/L | Standard Error 0.01801 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Free Fatty Acids | -0.0730 mmol/L | Standard Error 0.01816 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Free Fatty Acids | -0.1125 mmol/L | Standard Error 0.01787 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Free Fatty Acids | -0.1228 mmol/L | Standard Error 0.01787 |
Secondary
Change From Baseline to Week 26 in HDL Particles
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.02 μmol/L | Standard Error 0.208 |
| Pioglitazone Alone | Change From Baseline to Week 26 in HDL Particles | Small Particles | 0.00 μmol/L | Standard Error 0.441 |
| Pioglitazone Alone | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.13 μmol/L | Standard Error 0.33 |
| Pioglitazone Alone | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.18 μmol/L | Standard Error 0.397 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.16 μmol/L | Standard Error 0.336 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.43 μmol/L | Standard Error 0.405 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Small Particles | 0.41 μmol/L | Standard Error 0.45 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Large Particles | -0.16 μmol/L | Standard Error 0.212 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Small Particles | 0.10 μmol/L | Standard Error 0.444 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Total Particles | 1.03 μmol/L | Standard Error 0.4 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.54 μmol/L | Standard Error 0.332 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.39 μmol/L | Standard Error 0.21 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.81 μmol/L | Standard Error 0.338 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.37 μmol/L | Standard Error 0.407 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -0.78 μmol/L | Standard Error 0.452 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.53 μmol/L | Standard Error 0.213 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.86 μmol/L | Standard Error 0.332 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.55 μmol/L | Standard Error 0.21 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.77 μmol/L | Standard Error 0.4 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -0.68 μmol/L | Standard Error 0.444 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 1.31 μmol/L | Standard Error 0.4 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.75 μmol/L | Standard Error 0.21 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.67 μmol/L | Standard Error 0.332 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -0.17 μmol/L | Standard Error 0.444 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -1.35 μmol/L | Standard Error 0.452 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.67 μmol/L | Standard Error 0.407 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.64 μmol/L | Standard Error 0.213 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 1.48 μmol/L | Standard Error 0.338 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -1.47 μmol/L | Standard Error 0.448 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 1.13 μmol/L | Standard Error 0.212 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 1.47 μmol/L | Standard Error 0.335 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 1.15 μmol/L | Standard Error 0.403 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -2.77 μmol/L | Standard Error 0.452 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 1.34 μmol/L | Standard Error 0.213 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 1.69 μmol/L | Standard Error 0.337 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.26 μmol/L | Standard Error 0.406 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -2.21 μmol/L | Standard Error 0.452 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.83 μmol/L | Standard Error 0.407 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 1.26 μmol/L | Standard Error 0.213 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 1.71 μmol/L | Standard Error 0.337 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 0.96 μmol/L | Standard Error 0.331 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -0.40 μmol/L | Standard Error 0.443 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 1.61 μmol/L | Standard Error 0.398 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 1.02 μmol/L | Standard Error 0.209 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Medium Particles | 2.01 μmol/L | Standard Error 0.33 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Total Particles | 0.77 μmol/L | Standard Error 0.398 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Large Particles | 0.95 μmol/L | Standard Error 0.209 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in HDL Particles | Small Particles | -2.24 μmol/L | Standard Error 0.442 |
Secondary
Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 0.5 mg/dL | Standard Error 0.71 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 0.6 mg/dL | Standard Error 0.72 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 1.3 mg/dL | Standard Error 0.71 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 3.8 mg/dL | Standard Error 0.71 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 4.2 mg/dL | Standard Error 0.7 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 4.1 mg/dL | Standard Error 0.7 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 5.5 mg/dL | Standard Error 0.71 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 6.0 mg/dL | Standard Error 0.7 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 5.0 mg/dL | Standard Error 0.71 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 0.7 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 6.2 mg/dL | Standard Error 0.71 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol | 6.0 mg/dL | Standard Error 0.71 |
Secondary
Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -0.0550 mg/L | Standard Error 0.79868 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -0.6606 mg/L | Standard Error 0.80145 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | 0.2618 mg/L | Standard Error 0.79488 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | 0.2375 mg/L | Standard Error 0.80439 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -1.2490 mg/L | Standard Error 0.78817 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -0.9438 mg/L | Standard Error 0.79442 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -1.0480 mg/L | Standard Error 0.79805 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -1.1725 mg/L | Standard Error 0.79206 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | 0.1697 mg/L | Standard Error 0.80434 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -1.8562 mg/L | Standard Error 0.80771 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -2.8933 mg/L | Standard Error 0.79515 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein | -2.2191 mg/L | Standard Error 0.7945 |
Secondary
Change From Baseline to Week 26 in IDL Particles
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in IDL Particles | 5.1 nmol/L | Standard Error 3.65 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in IDL Particles | -7.3 nmol/L | Standard Error 3.73 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in IDL Particles | -3.2 nmol/L | Standard Error 3.68 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in IDL Particles | 5.2 nmol/L | Standard Error 3.74 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in IDL Particles | -2.4 nmol/L | Standard Error 3.67 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in IDL Particles | 0.0 nmol/L | Standard Error 3.68 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in IDL Particles | 3.0 nmol/L | Standard Error 3.74 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in IDL Particles | -5.0 nmol/L | Standard Error 3.71 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in IDL Particles | -5.5 nmol/L | Standard Error 3.74 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in IDL Particles | 0.1 nmol/L | Standard Error 3.74 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in IDL Particles | -5.0 nmol/L | Standard Error 3.66 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in IDL Particles | 1.0 nmol/L | Standard Error 3.66 |
Secondary
Change From Baseline to Week 26 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Insulin Levels | 6.78 µIU/mL | Standard Error 2.071 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Insulin Levels | 1.33 µIU/mL | Standard Error 2.096 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Insulin Levels | 1.43 µIU/mL | Standard Error 2.063 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Insulin Levels | -0.78 µIU/mL | Standard Error 2.078 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Insulin Levels | -3.05 µIU/mL | Standard Error 2.078 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Insulin Levels | -0.76 µIU/mL | Standard Error 2.087 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Insulin Levels | -2.56 µIU/mL | Standard Error 2.114 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Insulin Levels | -0.76 µIU/mL | Standard Error 2.152 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Insulin Levels | -1.42 µIU/mL | Standard Error 2.105 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Insulin Levels | -1.88 µIU/mL | Standard Error 2.105 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Insulin Levels | -2.33 µIU/mL | Standard Error 2.132 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Insulin Levels | -2.79 µIU/mL | Standard Error 2.096 |
Secondary
Change From Baseline to Week 26 in LDL Particles
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in LDL Particles | Total Particles | 15.0 nmol/L | Standard Error 30.11 |
| Pioglitazone Alone | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | 24.0 nmol/L | Standard Error 29.13 |
| Pioglitazone Alone | Change From Baseline to Week 26 in LDL Particles | Large Particles | -23.8 nmol/L | Standard Error 18.77 |
| Pioglitazone Alone | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | 9.1 nmol/L | Standard Error 7.14 |
| Pioglitazone Alone | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | 32.4 nmol/L | Standard Error 35.72 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | 2.5 nmol/L | Standard Error 29.71 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Total Particles | -14.5 nmol/L | Standard Error 30.73 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | 2.2 nmol/L | Standard Error 36.44 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Large Particles | -12.3 nmol/L | Standard Error 19.14 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | 0.0 nmol/L | Standard Error 7.28 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -36.6 nmol/L | Standard Error 29.36 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -42.9 nmol/L | Standard Error 36 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Large Particles | 15.3 nmol/L | Standard Error 18.91 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Total Particles | -30.8 nmol/L | Standard Error 30.36 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -6.9 nmol/L | Standard Error 7.2 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -122.5 nmol/L | Standard Error 36.59 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -96.3 nmol/L | Standard Error 29.84 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 70.5 nmol/L | Standard Error 19.22 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -25.8 nmol/L | Standard Error 7.31 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -46.3 nmol/L | Standard Error 30.86 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -115.1 nmol/L | Standard Error 30.35 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 63.2 nmol/L | Standard Error 18.9 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -175.1 nmol/L | Standard Error 35.99 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -29.9 nmol/L | Standard Error 7.19 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -145.7 nmol/L | Standard Error 29.35 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -119.4 nmol/L | Standard Error 30.37 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 93.1 nmol/L | Standard Error 18.9 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -36.2 nmol/L | Standard Error 7.2 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -174.5 nmol/L | Standard Error 29.37 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -211.5 nmol/L | Standard Error 36.01 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -30.0 nmol/L | Standard Error 7.32 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -68.6 nmol/L | Standard Error 30.9 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 79.3 nmol/L | Standard Error 19.27 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -154.9 nmol/L | Standard Error 36.6 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -124.9 nmol/L | Standard Error 29.85 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -47.4 nmol/L | Standard Error 7.26 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 96.6 nmol/L | Standard Error 19.09 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -248.7 nmol/L | Standard Error 36.31 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -201.6 nmol/L | Standard Error 29.61 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -158.9 nmol/L | Standard Error 30.62 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -55.0 nmol/L | Standard Error 7.31 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -209.4 nmol/L | Standard Error 30.85 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -304.9 nmol/L | Standard Error 36.58 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -250.0 nmol/L | Standard Error 29.83 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 102.7 nmol/L | Standard Error 19.22 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -209.6 nmol/L | Standard Error 29.83 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 137.7 nmol/L | Standard Error 19.23 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -47.1 nmol/L | Standard Error 7.31 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -119.7 nmol/L | Standard Error 30.87 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -256.9 nmol/L | Standard Error 36.58 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -223.6 nmol/L | Standard Error 29.22 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -57.6 nmol/L | Standard Error 7.16 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 121.9 nmol/L | Standard Error 18.83 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -164.6 nmol/L | Standard Error 30.22 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -281.1 nmol/L | Standard Error 35.82 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Medium-Small Particles | -57.8 nmol/L | Standard Error 7.17 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Particles | -219.9 nmol/L | Standard Error 30.21 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Large Particles | 122.7 nmol/L | Standard Error 18.83 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Total Small Particles | -341.3 nmol/L | Standard Error 35.82 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in LDL Particles | Very Small Particles | -283.9 nmol/L | Standard Error 29.21 |
Secondary
Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 3.6 mg/dL | Standard Error 2.43 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 2.8 mg/dL | Standard Error 2.47 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 3.6 mg/dL | Standard Error 2.44 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 7.9 mg/dL | Standard Error 2.41 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 3.7 mg/dL | Standard Error 2.38 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 6.1 mg/dL | Standard Error 2.41 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 6.2 mg/dL | Standard Error 2.43 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 2.9 mg/dL | Standard Error 2.4 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 3.0 mg/dL | Standard Error 2.43 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 8.1 mg/dL | Standard Error 2.4 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 9.1 mg/dL | Standard Error 2.43 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol | 7.7 mg/dL | Standard Error 2.39 |
Secondary
Change From Baseline to Week 26 in Mean HDL Particle Size
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.03 nm | Standard Error 0.025 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.00 nm | Standard Error 0.025 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.07 nm | Standard Error 0.025 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.06 nm | Standard Error 0.025 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.06 nm | Standard Error 0.025 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.11 nm | Standard Error 0.025 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.10 nm | Standard Error 0.025 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.15 nm | Standard Error 0.025 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.20 nm | Standard Error 0.025 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.19 nm | Standard Error 0.025 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.16 nm | Standard Error 0.025 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean HDL Particle Size | 0.19 nm | Standard Error 0.025 |
Secondary
Change From Baseline to Week 26 in Mean LDL Particle Size
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Mean LDL Particle Size | -0.06 nm | Standard Error 0.061 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Mean LDL Particle Size | -0.01 nm | Standard Error 0.062 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.07 nm | Standard Error 0.061 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.26 nm | Standard Error 0.062 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.38 nm | Standard Error 0.061 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.41 nm | Standard Error 0.061 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.38 nm | Standard Error 0.062 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.48 nm | Standard Error 0.062 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.57 nm | Standard Error 0.062 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.59 nm | Standard Error 0.062 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.55 nm | Standard Error 0.061 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean LDL Particle Size | 0.63 nm | Standard Error 0.061 |
Secondary
Change From Baseline to Week 26 in Mean VLDL Particle Size
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Mean VLDL Particle Size | 0.26 nm | Standard Error 0.685 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Mean VLDL Particle Size | 0.52 nm | Standard Error 0.7 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Mean VLDL Particle Size | 0.35 nm | Standard Error 0.691 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -2.99 nm | Standard Error 0.703 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -2.66 nm | Standard Error 0.694 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -2.36 nm | Standard Error 0.691 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -2.88 nm | Standard Error 0.703 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -3.69 nm | Standard Error 0.697 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -3.30 nm | Standard Error 0.702 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -1.60 nm | Standard Error 0.703 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -4.65 nm | Standard Error 0.688 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Mean VLDL Particle Size | -4.12 nm | Standard Error 0.688 |
Secondary
Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | 12.4 mg/dL | Standard Error 7.26 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | 7.3 mg/dL | Standard Error 7.42 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -6.8 mg/dL | Standard Error 7.32 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -18.9 mg/dL | Standard Error 7.44 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -20.4 mg/dL | Standard Error 7.32 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -23.1 mg/dL | Standard Error 7.32 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -6.9 mg/dL | Standard Error 7.44 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -23.5 mg/dL | Standard Error 7.38 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -19.7 mg/dL | Standard Error 7.44 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -8.6 mg/dL | Standard Error 7.44 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -32.1 mg/dL | Standard Error 7.29 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides | -25.8 mg/dL | Standard Error 7.29 |
Secondary
Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -3.00 ng/mL | Standard Error 3.526 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | 0.57 ng/mL | Standard Error 3.54 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -3.29 ng/mL | Standard Error 3.481 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -5.43 ng/mL | Standard Error 3.529 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -4.75 ng/mL | Standard Error 3.465 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -9.62 ng/mL | Standard Error 3.51 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -5.24 ng/mL | Standard Error 3.495 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | 1.89 ng/mL | Standard Error 3.511 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -6.66 ng/mL | Standard Error 3.525 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -3.02 ng/mL | Standard Error 3.622 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -5.22 ng/mL | Standard Error 3.466 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 | -11.48 ng/mL | Standard Error 3.496 |
Secondary
Change From Baseline to Week 26 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.007 ratio | Standard Error 0.0151 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.001 ratio | Standard Error 0.0153 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.064 ratio | Standard Error 0.0151 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.038 ratio | Standard Error 0.0152 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.071 ratio | Standard Error 0.0152 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.063 ratio | Standard Error 0.0152 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.030 ratio | Standard Error 0.0154 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.081 ratio | Standard Error 0.0159 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.072 ratio | Standard Error 0.0154 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.014 ratio | Standard Error 0.0154 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.109 ratio | Standard Error 0.0156 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Proinsulin/Insulin Ratio | -0.092 ratio | Standard Error 0.0153 |
Secondary
Change From Baseline to Week 26 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Total Cholesterol Levels | 4.4 mg/dL | Standard Error 2.82 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Total Cholesterol Levels | 2.2 mg/dL | Standard Error 2.85 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Total Cholesterol Levels | 0.9 mg/dL | Standard Error 2.84 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Total Cholesterol Levels | 5.8 mg/dL | Standard Error 2.81 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Total Cholesterol Levels | 4.3 mg/dL | Standard Error 2.78 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Total Cholesterol Levels | 3.5 mg/dL | Standard Error 2.79 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Total Cholesterol Levels | 8.8 mg/dL | Standard Error 2.84 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Total Cholesterol Levels | 2.8 mg/dL | Standard Error 2.8 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Total Cholesterol Levels | 3.2 mg/dL | Standard Error 2.83 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Total Cholesterol Levels | 9.5 mg/dL | Standard Error 2.8 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Total Cholesterol Levels | 6.0 mg/dL | Standard Error 2.81 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Total Cholesterol Levels | 5.1 mg/dL | Standard Error 2.81 |
Secondary
Change From Baseline to Week 26 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in Triglyceride Levels | 3.7 mg/dL | Standard Error 7.65 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in Triglyceride Levels | -1.1 mg/dL | Standard Error 7.74 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in Triglyceride Levels | -15.2 mg/dL | Standard Error 7.71 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in Triglyceride Levels | -29.5 mg/dL | Standard Error 7.65 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in Triglyceride Levels | -37.7 mg/dL | Standard Error 7.56 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in Triglyceride Levels | -38.5 mg/dL | Standard Error 7.59 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in Triglyceride Levels | -27.0 mg/dL | Standard Error 7.71 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in Triglyceride Levels | -37.3 mg/dL | Standard Error 7.59 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in Triglyceride Levels | -33.5 mg/dL | Standard Error 7.68 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in Triglyceride Levels | -32.4 mg/dL | Standard Error 7.62 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in Triglyceride Levels | -49.3 mg/dL | Standard Error 7.65 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in Triglyceride Levels | -50.1 mg/dL | Standard Error 7.65 |
Secondary
Change From Baseline to Week 26 in VLDL / Chylomicron Particles
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | 2.80 nmol/L | Standard Error 3.379 |
| Pioglitazone Alone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | 1.31 nmol/L | Standard Error 0.577 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | 0.59 nmol/L | Standard Error 3.45 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | 0.94 nmol/L | Standard Error 0.589 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -5.79 nmol/L | Standard Error 3.405 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -0.14 nmol/L | Standard Error 0.582 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -2.99 nmol/L | Standard Error 3.462 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -1.56 nmol/L | Standard Error 0.592 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -1.71 nmol/L | Standard Error 0.582 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -3.31 nmol/L | Standard Error 3.405 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -5.15 nmol/L | Standard Error 3.405 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -1.80 nmol/L | Standard Error 0.582 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -0.90 nmol/L | Standard Error 0.592 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | 3.68 nmol/L | Standard Error 3.464 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -0.59 nmol/L | Standard Error 3.436 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -2.24 nmol/L | Standard Error 0.587 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -0.35 nmol/L | Standard Error 3.463 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -1.79 nmol/L | Standard Error 0.592 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -3.83 nmol/L | Standard Error 3.463 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -0.67 nmol/L | Standard Error 0.592 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -2.80 nmol/L | Standard Error 0.58 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | -1.70 nmol/L | Standard Error 3.394 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Large Particles | -2.36 nmol/L | Standard Error 0.58 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Particles | Total Particles | 1.56 nmol/L | Standard Error 3.392 |
Secondary
Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | 11.9 mg/dL | Standard Error 7.23 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | 8.3 mg/dL | Standard Error 7.39 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -7.0 mg/dL | Standard Error 7.29 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -20.4 mg/dL | Standard Error 7.41 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -20.4 mg/dL | Standard Error 7.29 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -23.8 mg/dL | Standard Error 7.29 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -8.2 mg/dL | Standard Error 7.41 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -23.5 mg/dL | Standard Error 7.35 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -18.9 mg/dL | Standard Error 7.41 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -10.4 mg/dL | Standard Error 7.41 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -32.3 mg/dL | Standard Error 7.26 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides | -26.2 mg/dL | Standard Error 7.26 |
Secondary
Change From Baseline to Week 26 in VLDL Particles
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates
Time frame: Baseline and Week 26
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | 1.54 nmol/L | Standard Error 2.275 |
| Pioglitazone Alone | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 0.26 nmol/L | Standard Error 1.831 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | 0.85 nmol/L | Standard Error 2.324 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 26 in VLDL Particles | Small Particles | -0.87 nmol/L | Standard Error 1.868 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -2.94 nmol/L | Standard Error 2.292 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 26 in VLDL Particles | Small Particles | -2.91 nmol/L | Standard Error 1.846 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -4.43 nmol/L | Standard Error 2.331 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 2.83 nmol/L | Standard Error 1.876 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | -0.19 nmol/L | Standard Error 1.845 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -1.78 nmol/L | Standard Error 2.293 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -5.42 nmol/L | Standard Error 2.292 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 1.90 nmol/L | Standard Error 1.845 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 4.16 nmol/L | Standard Error 1.877 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | 0.28 nmol/L | Standard Error 2.332 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -2.17 nmol/L | Standard Error 2.313 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 4.07 nmol/L | Standard Error 1.863 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -4.38 nmol/L | Standard Error 2.331 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 5.45 nmol/L | Standard Error 1.876 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -2.70 nmol/L | Standard Error 2.331 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | -0.08 nmol/L | Standard Error 1.878 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 6.77 nmol/L | Standard Error 1.837 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -5.09 nmol/L | Standard Error 2.285 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Small Particles | 8.33 nmol/L | Standard Error 1.837 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 26 in VLDL Particles | Medium Particles | -4.83 nmol/L | Standard Error 2.284 |
Secondary
Change From Baseline to Week 2 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 2
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 2 in Fasting Plasma Glucose | 4.8 mg/dL | Standard Error 2.78 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 2 in Fasting Plasma Glucose | -21.9 mg/dL | Standard Error 2.88 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 2 in Fasting Plasma Glucose | -18.9 mg/dL | Standard Error 2.82 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -10.4 mg/dL | Standard Error 2.8 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -30.1 mg/dL | Standard Error 2.8 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -31.7 mg/dL | Standard Error 2.78 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -4.3 mg/dL | Standard Error 2.83 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -30.0 mg/dL | Standard Error 2.79 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -31.3 mg/dL | Standard Error 2.81 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -19.3 mg/dL | Standard Error 2.79 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -30.8 mg/dL | Standard Error 2.79 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 2 in Fasting Plasma Glucose | -31.7 mg/dL | Standard Error 2.81 |
Secondary
Change From Baseline to Week 4 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in C-peptide Levels | 0.002 ng/mL | Standard Error 0.0705 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in C-peptide Levels | -0.032 ng/mL | Standard Error 0.0727 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in C-peptide Levels | 0.076 ng/mL | Standard Error 0.0734 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in C-peptide Levels | -0.246 ng/mL | Standard Error 0.073 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in C-peptide Levels | -0.248 ng/mL | Standard Error 0.0714 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in C-peptide Levels | -0.238 ng/mL | Standard Error 0.072 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in C-peptide Levels | -0.232 ng/mL | Standard Error 0.0721 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in C-peptide Levels | -0.259 ng/mL | Standard Error 0.0718 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in C-peptide Levels | -0.268 ng/mL | Standard Error 0.0705 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in C-peptide Levels | -0.393 ng/mL | Standard Error 0.0714 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in C-peptide Levels | -0.252 ng/mL | Standard Error 0.0734 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in C-peptide Levels | -0.337 ng/mL | Standard Error 0.0738 |
Secondary
Change From Baseline to Week 4 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Fasting Plasma Glucose | 3.8 mg/dL | Standard Error 2.87 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Fasting Plasma Glucose | -20.4 mg/dL | Standard Error 2.95 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Fasting Plasma Glucose | -22.8 mg/dL | Standard Error 2.92 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -20.2 mg/dL | Standard Error 2.9 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -35.3 mg/dL | Standard Error 2.87 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -37.3 mg/dL | Standard Error 2.86 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -13.4 mg/dL | Standard Error 2.92 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -37.4 mg/dL | Standard Error 2.88 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -36.0 mg/dL | Standard Error 2.91 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -26.1 mg/dL | Standard Error 2.87 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -37.8 mg/dL | Standard Error 2.89 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Plasma Glucose | -46.2 mg/dL | Standard Error 2.89 |
Secondary
Change From Baseline to Week 4 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Fasting Proinsulin | -0.1 pmol/L | Standard Error 1.36 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Fasting Proinsulin | -4.7 pmol/L | Standard Error 1.39 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Fasting Proinsulin | -2.3 pmol/L | Standard Error 1.41 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Proinsulin | -4.8 pmol/L | Standard Error 1.42 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Proinsulin | -9.9 pmol/L | Standard Error 1.41 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Fasting Proinsulin | -8.9 pmol/L | Standard Error 1.41 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Proinsulin | -6.7 pmol/L | Standard Error 1.4 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Proinsulin | -9.6 pmol/L | Standard Error 1.43 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Fasting Proinsulin | -9.5 pmol/L | Standard Error 1.37 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Proinsulin | -7.2 pmol/L | Standard Error 1.39 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Proinsulin | -11.3 pmol/L | Standard Error 1.43 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Fasting Proinsulin | -11.7 pmol/L | Standard Error 1.44 |
Secondary
Change From Baseline to Week 4 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in HbA1c | -0.22 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in HbA1c | -0.46 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in HbA1c | -0.51 percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in HbA1c | -0.32 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in HbA1c | -0.53 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in HbA1c | -0.61 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in HbA1c | -0.24 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in HbA1c | -0.60 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in HbA1c | -0.60 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in HbA1c | -0.40 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in HbA1c | -0.58 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in HbA1c | -0.63 percentage of glycosylated hemoglobin | Standard Error 0.04 |
Secondary
Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | -0.4 mg/dL | Standard Error 0.57 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | -0.6 mg/dL | Standard Error 0.59 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | -0.5 mg/dL | Standard Error 0.59 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 2.5 mg/dL | Standard Error 0.59 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 1.6 mg/dL | Standard Error 0.58 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 1.6 mg/dL | Standard Error 0.57 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 3.2 mg/dL | Standard Error 0.57 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 2.3 mg/dL | Standard Error 0.56 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 3.5 mg/dL | Standard Error 0.57 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 3.3 mg/dL | Standard Error 0.58 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 4.2 mg/dL | Standard Error 0.58 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol | 5.1 mg/dL | Standard Error 0.59 |
Secondary
Change From Baseline to Week 4 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Insulin Levels | 1.06 µIU/mL | Standard Error 0.737 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Insulin Levels | -0.33 µIU/mL | Standard Error 0.756 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Insulin Levels | 2.31 µIU/mL | Standard Error 0.771 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Insulin Levels | -1.68 µIU/mL | Standard Error 0.767 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Insulin Levels | -3.03 µIU/mL | Standard Error 0.76 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Insulin Levels | -1.86 µIU/mL | Standard Error 0.763 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Insulin Levels | -2.43 µIU/mL | Standard Error 0.76 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Insulin Levels | -1.45 µIU/mL | Standard Error 0.779 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Insulin Levels | -2.05 µIU/mL | Standard Error 0.743 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Insulin Levels | -2.76 µIU/mL | Standard Error 0.76 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Insulin Levels | -1.85 µIU/mL | Standard Error 0.774 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Insulin Levels | -2.65 µIU/mL | Standard Error 0.778 |
Secondary
Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 2.1 mg/dL | Standard Error 2.11 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | -2.4 mg/dL | Standard Error 2.22 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 1.4 mg/dL | Standard Error 2.19 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 2.6 mg/dL | Standard Error 2.16 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 1.6 mg/dL | Standard Error 2.12 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | -2.7 mg/dL | Standard Error 2.11 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 3.2 mg/dL | Standard Error 2.12 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | -2.8 mg/dL | Standard Error 2.09 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 0.4 mg/dL | Standard Error 2.1 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | 3.4 mg/dL | Standard Error 2.13 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | -0.3 mg/dL | Standard Error 2.15 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol | -3.4 mg/dL | Standard Error 2.13 |
Secondary
Change From Baseline to Week 4 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.015 ratio | Standard Error 0.0147 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.039 ratio | Standard Error 0.0151 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.058 ratio | Standard Error 0.0154 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.029 ratio | Standard Error 0.0153 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.054 ratio | Standard Error 0.0153 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.054 ratio | Standard Error 0.0153 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.023 ratio | Standard Error 0.0152 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.068 ratio | Standard Error 0.0157 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.045 ratio | Standard Error 0.0149 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.009 ratio | Standard Error 0.0152 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.111 ratio | Standard Error 0.0155 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Proinsulin/Insulin Ratio | -0.072 ratio | Standard Error 0.0156 |
Secondary
Change From Baseline to Week 4 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Total Cholesterol Levels | 1.3 mg/dL | Standard Error 2.4 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Total Cholesterol Levels | -3.8 mg/dL | Standard Error 2.47 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Total Cholesterol Levels | -3.7 mg/dL | Standard Error 2.48 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Total Cholesterol Levels | 2.1 mg/dL | Standard Error 2.47 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Total Cholesterol Levels | -2.3 mg/dL | Standard Error 2.42 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Total Cholesterol Levels | -10.2 mg/dL | Standard Error 2.41 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Total Cholesterol Levels | 3.7 mg/dL | Standard Error 2.42 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Total Cholesterol Levels | -7.2 mg/dL | Standard Error 2.38 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Total Cholesterol Levels | -2.7 mg/dL | Standard Error 2.41 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Total Cholesterol Levels | -1.2 mg/dL | Standard Error 2.43 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Total Cholesterol Levels | -3.6 mg/dL | Standard Error 2.43 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Total Cholesterol Levels | -6.7 mg/dL | Standard Error 2.47 |
Secondary
Change From Baseline to Week 4 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 4
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 4 in Triglyceride Levels | -2.4 mg/dL | Standard Error 6.93 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 4 in Triglyceride Levels | -2.2 mg/dL | Standard Error 7.15 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 4 in Triglyceride Levels | -25.0 mg/dL | Standard Error 7.18 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 4 in Triglyceride Levels | -21.5 mg/dL | Standard Error 7.14 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 4 in Triglyceride Levels | -35.8 mg/dL | Standard Error 6.99 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 4 in Triglyceride Levels | -51.1 mg/dL | Standard Error 6.96 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 4 in Triglyceride Levels | -26.7 mg/dL | Standard Error 6.99 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 4 in Triglyceride Levels | -42.2 mg/dL | Standard Error 6.88 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 4 in Triglyceride Levels | -44.4 mg/dL | Standard Error 6.96 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 4 in Triglyceride Levels | -47.1 mg/dL | Standard Error 7.02 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 4 in Triglyceride Levels | -39.2 mg/dL | Standard Error 7.03 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 4 in Triglyceride Levels | -49.1 mg/dL | Standard Error 7.15 |
Secondary
Change From Baseline to Week 8 in Body Weight
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Body Weight | -0.13 kg | Standard Error 0.176 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Body Weight | -0.05 kg | Standard Error 0.179 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Body Weight | -0.45 kg | Standard Error 0.178 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Body Weight | 0.32 kg | Standard Error 0.177 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Body Weight | 0.09 kg | Standard Error 0.174 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Body Weight | 0.22 kg | Standard Error 0.176 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Body Weight | 0.57 kg | Standard Error 0.177 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Body Weight | 0.49 kg | Standard Error 0.174 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Body Weight | 0.74 kg | Standard Error 0.177 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Body Weight | 0.46 kg | Standard Error 0.179 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Body Weight | 0.43 kg | Standard Error 0.177 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Body Weight | 0.93 kg | Standard Error 0.175 |
Secondary
Change From Baseline to Week 8 in C-peptide Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in C-peptide Levels | -0.044 ng/mL | Standard Error 0.0798 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in C-peptide Levels | 0.114 ng/mL | Standard Error 0.0807 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in C-peptide Levels | 0.108 ng/mL | Standard Error 0.0801 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in C-peptide Levels | -0.221 ng/mL | Standard Error 0.0798 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in C-peptide Levels | -0.315 ng/mL | Standard Error 0.0798 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in C-peptide Levels | -0.261 ng/mL | Standard Error 0.0801 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in C-peptide Levels | -0.380 ng/mL | Standard Error 0.0814 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in C-peptide Levels | -0.365 ng/mL | Standard Error 0.0802 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in C-peptide Levels | -0.207 ng/mL | Standard Error 0.0797 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in C-peptide Levels | -0.467 ng/mL | Standard Error 0.0798 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in C-peptide Levels | -0.300 ng/mL | Standard Error 0.0814 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in C-peptide Levels | -0.464 ng/mL | Standard Error 0.0798 |
Secondary
Change From Baseline to Week 8 in Fasting Plasma Glucose
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Fasting Plasma Glucose | 5.7 mg/dL | Standard Error 3.05 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Fasting Plasma Glucose | -19.5 mg/dL | Standard Error 3.14 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Fasting Plasma Glucose | -19.3 mg/dL | Standard Error 3.09 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -22.2 mg/dL | Standard Error 3.07 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -42.3 mg/dL | Standard Error 3.05 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -39.3 mg/dL | Standard Error 3.04 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -24.0 mg/dL | Standard Error 3.1 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -40.5 mg/dL | Standard Error 3.05 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -44.1 mg/dL | Standard Error 3.08 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -35.6 mg/dL | Standard Error 3.05 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -44.0 mg/dL | Standard Error 3.06 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Plasma Glucose | -52.3 mg/dL | Standard Error 3.07 |
Secondary
Change From Baseline to Week 8 in Fasting Proinsulin
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Fasting Proinsulin | 0.7 pmol/L | Standard Error 1.48 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Fasting Proinsulin | 0.2 pmol/L | Standard Error 1.5 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Fasting Proinsulin | -2.6 pmol/L | Standard Error 1.48 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Proinsulin | -3.8 pmol/L | Standard Error 1.49 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Proinsulin | -11.1 pmol/L | Standard Error 1.5 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Fasting Proinsulin | -10.7 pmol/L | Standard Error 1.5 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Proinsulin | -8.8 pmol/L | Standard Error 1.52 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Proinsulin | -11.8 pmol/L | Standard Error 1.54 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Fasting Proinsulin | -9.4 pmol/L | Standard Error 1.5 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Proinsulin | -9.0 pmol/L | Standard Error 1.5 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Proinsulin | -11.0 pmol/L | Standard Error 1.53 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Fasting Proinsulin | -13.8 pmol/L | Standard Error 1.5 |
Secondary
Change From Baseline to Week 8 in HbA1c
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in HbA1c | -0.30 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in HbA1c | -0.75 percentage of glycosylated hemoglobin | Standard Error 0.059 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in HbA1c | -0.80 percentage of glycosylated hemoglobin | Standard Error 0.059 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in HbA1c | -0.50 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in HbA1c | -1.01 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in HbA1c | -1.04 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in HbA1c | -0.57 percentage of glycosylated hemoglobin | Standard Error 0.059 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in HbA1c | -1.05 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in HbA1c | -1.02 percentage of glycosylated hemoglobin | Standard Error 0.059 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in HbA1c | -0.76 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in HbA1c | -1.11 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in HbA1c | -1.20 percentage of glycosylated hemoglobin | Standard Error 0.058 |
Secondary
Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | -0.5 mg/dL | Standard Error 0.6 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | -0.1 mg/dL | Standard Error 0.61 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 0.6 mg/dL | Standard Error 0.61 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 2.8 mg/dL | Standard Error 0.6 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 2.3 mg/dL | Standard Error 0.59 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 2.9 mg/dL | Standard Error 0.6 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 4.8 mg/dL | Standard Error 0.61 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 4.2 mg/dL | Standard Error 0.6 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 4.6 mg/dL | Standard Error 0.6 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 4.5 mg/dL | Standard Error 0.6 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 5.7 mg/dL | Standard Error 0.6 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol | 6.3 mg/dL | Standard Error 0.6 |
Secondary
Change From Baseline to Week 8 in Insulin Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Insulin Levels | -0.46 µIU/mL | Standard Error 0.912 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Insulin Levels | 1.80 µIU/mL | Standard Error 0.923 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Insulin Levels | 1.69 µIU/mL | Standard Error 0.909 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Insulin Levels | -1.47 µIU/mL | Standard Error 0.916 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Insulin Levels | -2.21 µIU/mL | Standard Error 0.923 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Insulin Levels | -2.78 µIU/mL | Standard Error 0.923 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Insulin Levels | -2.74 µIU/mL | Standard Error 0.935 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Insulin Levels | -3.15 µIU/mL | Standard Error 0.953 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Insulin Levels | -1.20 µIU/mL | Standard Error 0.927 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Insulin Levels | -2.83 µIU/mL | Standard Error 0.927 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Insulin Levels | -1.96 µIU/mL | Standard Error 0.939 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Insulin Levels | -3.09 µIU/mL | Standard Error 0.924 |
Secondary
Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 9.4 mg/dL | Standard Error 2.24 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 2.1 mg/dL | Standard Error 2.3 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 3.4 mg/dL | Standard Error 2.24 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 7.3 mg/dL | Standard Error 2.21 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | -0.4 mg/dL | Standard Error 2.21 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 1.0 mg/dL | Standard Error 2.21 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 5.4 mg/dL | Standard Error 2.24 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 2.4 mg/dL | Standard Error 2.21 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 2.7 mg/dL | Standard Error 2.24 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 4.8 mg/dL | Standard Error 2.21 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | 2.0 mg/dL | Standard Error 2.24 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol | -3.2 mg/dL | Standard Error 2.2 |
Secondary
Change From Baseline to Week 8 in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | 0.005 ratio | Standard Error 0.0144 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.025 ratio | Standard Error 0.0146 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.045 ratio | Standard Error 0.0143 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.007 ratio | Standard Error 0.0144 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.086 ratio | Standard Error 0.0146 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.077 ratio | Standard Error 0.0146 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.036 ratio | Standard Error 0.0148 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.054 ratio | Standard Error 0.0152 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.072 ratio | Standard Error 0.0146 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.013 ratio | Standard Error 0.0146 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.098 ratio | Standard Error 0.0148 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Proinsulin/Insulin Ratio | -0.093 ratio | Standard Error 0.0146 |
Secondary
Change From Baseline to Week 8 in Total Cholesterol Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Total Cholesterol Levels | 10.9 mg/dL | Standard Error 2.46 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Total Cholesterol Levels | -1.4 mg/dL | Standard Error 2.5 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Total Cholesterol Levels | -0.3 mg/dL | Standard Error 2.48 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Total Cholesterol Levels | 7.3 mg/dL | Standard Error 2.46 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Total Cholesterol Levels | -2.3 mg/dL | Standard Error 2.43 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Total Cholesterol Levels | -4.1 mg/dL | Standard Error 2.44 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Total Cholesterol Levels | 6.6 mg/dL | Standard Error 2.48 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Total Cholesterol Levels | 0.1 mg/dL | Standard Error 2.45 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Total Cholesterol Levels | 0.3 mg/dL | Standard Error 2.47 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Total Cholesterol Levels | 0.3 mg/dL | Standard Error 2.45 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Total Cholesterol Levels | -3.1 mg/dL | Standard Error 2.46 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Total Cholesterol Levels | -6.2 mg/dL | Standard Error 2.46 |
Secondary
Change From Baseline to Week 8 in Triglyceride Levels
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time frame: Baseline and Week 8
Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Alone | Change From Baseline to Week 8 in Triglyceride Levels | 26.3 mg/dL | Standard Error 7.56 |
| Alogliptin 12.5 + Pioglitazone | Change From Baseline to Week 8 in Triglyceride Levels | -16.4 mg/dL | Standard Error 7.69 |
| Alogliptin 25 + Pioglitazone | Change From Baseline to Week 8 in Triglyceride Levels | -23.0 mg/dL | Standard Error 7.62 |
| Placebo + Pioglitazone 15 | Change From Baseline to Week 8 in Triglyceride Levels | -20.5 mg/dL | Standard Error 7.56 |
| Alogliptin 12.5 + Pioglitazone 15 | Change From Baseline to Week 8 in Triglyceride Levels | -30.1 mg/dL | Standard Error 7.47 |
| Alogliptin 25 + Pioglitazone 15 | Change From Baseline to Week 8 in Triglyceride Levels | -46.4 mg/dL | Standard Error 7.5 |
| Placebo + Pioglitazone 30 | Change From Baseline to Week 8 in Triglyceride Levels | -30.3 mg/dL | Standard Error 7.62 |
| Alogliptin 12.5 + Pioglitazone 30 | Change From Baseline to Week 8 in Triglyceride Levels | -43.1 mg/dL | Standard Error 7.51 |
| Alogliptin 25 + Pioglitazone 30 | Change From Baseline to Week 8 in Triglyceride Levels | -44.5 mg/dL | Standard Error 7.6 |
| Placebo + Pioglitazone 45 | Change From Baseline to Week 8 in Triglyceride Levels | -53.1 mg/dL | Standard Error 7.53 |
| Alogliptin 12.5 + Pioglitazone 45 | Change From Baseline to Week 8 in Triglyceride Levels | -60.1 mg/dL | Standard Error 7.57 |
| Alogliptin 25 + Pioglitazone 45 | Change From Baseline to Week 8 in Triglyceride Levels | -52.7 mg/dL | Standard Error 7.56 |
Secondary
Percentage of Participants Meeting Rescue Criteria
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: 1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; 4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time frame: From Week 1 to Week 26
Population: Full analysis set including patients with at least 1 postbaseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants Meeting Rescue Criteria | 32.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants Meeting Rescue Criteria | 14.5 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants Meeting Rescue Criteria | 12.8 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants Meeting Rescue Criteria | 10.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants Meeting Rescue Criteria | 4.7 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants Meeting Rescue Criteria | 3.9 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants Meeting Rescue Criteria | 15.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants Meeting Rescue Criteria | 4.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants Meeting Rescue Criteria | 4.9 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants Meeting Rescue Criteria | 8.7 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants Meeting Rescue Criteria | 2.4 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants Meeting Rescue Criteria | 1.6 percentage of participants |
Secondary
Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: 1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; 4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time frame: From Week 1 to Week 26.
Population: Full analysis set including patients with at least 1 postbaseline visit. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants Meeting Rescue Criteria (Grouped Analysis) | 11.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants Meeting Rescue Criteria (Grouped Analysis) | 3.9 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants Meeting Rescue Criteria (Grouped Analysis) | 3.4 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 31.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 57.8 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 66.7 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 61.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 86.2 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 79.2 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 68.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 86.9 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 83.8 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 72.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 83.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | 86.9 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis) | 67.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis) | 85.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis) | 83.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 16.3 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 33.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 47.3 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 36.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 69.2 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 66.9 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 46.5 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 73.1 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 69.2 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 54.3 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 73.1 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% | 72.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 5.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 15.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 28.7 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 21.7 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 41.5 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 46.2 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 27.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 45.4 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 46.2 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 34.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 50.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | 58.5 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis) | 27.6 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis) | 45.9 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis) | 50.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis) | 45.7 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis) | 71.8 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis) | 69.5 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.
Time frame: Baseline and Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 1.6 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 7.8 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 11.6 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 7.0 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 23.1 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 21.5 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 9.3 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 22.3 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 26.2 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 17.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 30.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% | 35.4 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Baseline and Week 26.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis) | 11.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis) | 25.4 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis) | 27.7 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 0.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 8.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 12.4 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 6.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 21.5 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 24.6 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 11.6 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 30.0 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 30.0 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 19.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 32.3 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | 33.1 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis) | 12.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis) | 27.9 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis) | 29.2 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 6.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 22.7 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 27.1 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 25.6 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 49.2 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 54.6 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 29.5 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 53.1 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 53.1 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 36.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 61.5 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7% | 60.0 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis) | 30.5 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis) | 54.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis) | 55.9 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 24.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 38.3 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 55.0 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 51.9 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 77.7 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 71.5 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 55.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 73.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 72.3 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 56.6 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 80.8 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | 78.5 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: Week 26
Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis) | 54.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis) | 77.4 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis) | 74.1 percentage of participants |
Secondary
Percentage of Participants With Marked Hyperglycemia
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
Time frame: From Week 1 to Week 26
Population: Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Marked Hyperglycemia | 60.5 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Marked Hyperglycemia | 42.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Marked Hyperglycemia | 39.7 percentage of participants |
| Placebo + Pioglitazone 15 | Percentage of Participants With Marked Hyperglycemia | 37.8 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 15 | Percentage of Participants With Marked Hyperglycemia | 27.1 percentage of participants |
| Alogliptin 25 + Pioglitazone 15 | Percentage of Participants With Marked Hyperglycemia | 22.3 percentage of participants |
| Placebo + Pioglitazone 30 | Percentage of Participants With Marked Hyperglycemia | 39.2 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 30 | Percentage of Participants With Marked Hyperglycemia | 26.4 percentage of participants |
| Alogliptin 25 + Pioglitazone 30 | Percentage of Participants With Marked Hyperglycemia | 23.6 percentage of participants |
| Placebo + Pioglitazone 45 | Percentage of Participants With Marked Hyperglycemia | 41.1 percentage of participants |
| Alogliptin 12.5 + Pioglitazone 45 | Percentage of Participants With Marked Hyperglycemia | 20.3 percentage of participants |
| Alogliptin 25 + Pioglitazone 45 | Percentage of Participants With Marked Hyperglycemia | 20.5 percentage of participants |
Secondary
Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time frame: From Week 1 to Week 26
Population: Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone Alone | Percentage of Participants With Marked Hyperglycemia (Grouped Analysis) | 39.4 percentage of participants |
| Alogliptin 12.5 + Pioglitazone | Percentage of Participants With Marked Hyperglycemia (Grouped Analysis) | 24.6 percentage of participants |
| Alogliptin 25 + Pioglitazone | Percentage of Participants With Marked Hyperglycemia (Grouped Analysis) | 22.1 percentage of participants |