Diabetes Mellitus
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Hyperglycemia, Drug Therapy
Brief summary
The purpose of the study is to compare the effect of adding alogliptin, once daily (QD), to the ongoing treatment regimen of pioglitazone HCl and metformin in patients with inadequate glycemic control.
Detailed description
Despite the introduction of new classes of medications for glycemic control, just over half of adults with type 2 diabetes mellitus (T2DM) achieve a glycosylated hemoglobin level less than 7.0%, the American Diabetes Association recommended glycosylated hemoglobin goal. The rising incidence of type 2 diabetes mellitus along with limitations of the currently available treatments suggest the need for new therapies for glycemic control along with the increased requirement for combination therapy in type 2 diabetes mellitus. Thiazolidinediones increase glucose utilization, decrease gluconeogenesis, and increase glucose disposal through an incompletely understood mechanism but one associated with binding of the drug to nuclear receptors known as peroxisome proliferator-activated receptors-gamma. Peroxisome proliferator-activated receptors-gamma are found in tissues important for insulin action, such as adipose tissue, skeletal muscle, and the liver. The greatest concentration of peroxisome proliferator-activated receptors-gamma receptors is in adipose tissue. Thiazolidinediones reduce insulin resistance by enhancing insulin sensitivity in muscle cells, adipose tissue, and hepatic cells (inhibiting hepatic gluconeogenesis) with no direct impact on insulin secretion. Thus, thiazolidinediones improve glycemic control and result in reduced levels of circulating insulin. Pioglitazone HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan). Pioglitazone depends on the presence of insulin for its mechanism of action. Worldwide clinical investigation has shown that, as an adjunct to diet and exercise, pioglitazone improves glycemic control when used as monotherapy, and in combination with commonly used antidiabetic medications (ie, sulfonylureas, metformin, or insulin). SYR-322 (alogliptin) is a selective, orally available inhibitor of dipeptidyl peptidase IV currently in development by Takeda Global Research & Development Center, Inc. as a treatment for type 2 diabetes mellitus. Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 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 β-cells to stimulate glucose-dependent insulin secretion and regulate β-cell proliferation and cytoprotection. Glucagon-like peptide-1 also inhibits gastric emptying, glucagon secretion, and food intake. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes. Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion) and pioglitazone (enhancement of insulin sensitivity) and the absence of overlapping safety risks, the introduction of this combination therapy in patients with T2DM could potentially show enhanced glycemic control and allow patients to reach and maintain their HbA1c goal more effectively. This study is designed to determine if the addition of alogliptin to a combination of pioglitazone with metformin can be effective at achieving glycemic control without increasing safety risks versus the titration of pioglitazone to 45 mg with metformin in patients with type 2 diabetes mellitus who are experiencing inadequate glycemic control on a current regimen of metformin.
Interventions
DRUGAlogliptin
Alogliptin tablets.
DRUGPioglitazone
Pioglitazone tablets.
DRUGMetformin
Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.
DRUGPlacebo
Matching placebo tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Has a historical diagnosis of type 2 diabetes mellitus. * Meets one of the following: * Has been inadequately controlled (HbA1c between 7% and 10%, inclusive) on a stable dose of greater than or equal to 1500 mg (or maximum tolerated dose) of metformin and 30 mg of pioglitazone * Has been inadequately controlled (as defined by an HbA1c ≥7.5%) on a combination therapy including metformin and another oral antidiabetic agent (ie, sulfonylureas, rosiglitazone maleate, or pioglitazone 15 mg, etc). Subjects on a combination therapy that included a DPP-4 inhibitor were excluded. * No treatment with antidiabetic agents other than metformin and pioglitazone. * Body mass index greater than or equal to 23 kg/m\^2 and less than or equal to 45 kg/m\^2. * Fasting plasma C-peptide concentration greater than or equal to 0.8 ng/mL. * Systolic blood pressure less than 160 mmHg and diastolic pressure less than 100 mmHg. * Hemoglobin greater than or equal to 12 g/dL for males and greater than or equal to 10 g/dL for females. * Alanine aminotransferase less than or equal to 2.5 x upper limit of normal. * Serum creatinine less than 1.5 mg/dL for males and less than 1.4 mg/dL for females. * Thyroid-stimulating hormone level less than or equal to the upper limit of normal range and the patient is 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 prohibits the patient from completing the study.
Exclusion criteria
* Urine albumin/creatinine ratio of greater than 1000 μg/mg. * History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. * History of bladder cancer. * History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. * Patients with unexplained microscopic hematuria of greater than +1, confirmed by repeat testing. * History of treated diabetic gastroparesis. * History of gastric bypass surgery. * New York Heart Association Class I-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 that may affect determination of glycosylated hemoglobin. * History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. * History of a psychiatric disorder that will affect 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. * History of alcohol abuse or substance abuse within the 2 years prior to Screening. * Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening. * Prior treatment in an investigational study of alogliptin. * Hypersensitive to pioglitazone HCl, metformin, alogliptin or other excipients. * The patient has donated more than 400 mL of blood within the 90 days prior to Screening and Pre-Screening, if applicable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline and Weeks 26 and 52. | The change from Baseline to Week 26 and Week 52 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 |
|---|---|---|
| Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7%. |
| Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 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% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 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 ≥ 1.0% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 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% | Weeks 26 and 52. | Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%. |
| Change From Baseline in Fasting Plasma Glucose | Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52. | The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline FPG as covariates. |
| Percentage of Participants With Marked Hyperglycemia | Baseline to Week 52 | Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). |
| Percentage of Participants Meeting Hyperglycemic Rescue Criteria | Baseline to Week 52 | Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 7 days after the first sample and analyzed by the central laboratory: 1. After more than 2 weeks of treatment but prior to the Week 4 Visit: A single fasting plasma glucose (FPG) ≥275 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: A single FPG ≥250 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: A single FPG ≥225 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 the baseline HbA1c. |
| Change From Baseline in Fasting Proinsulin | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | 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, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin as covariates. |
| Change From Baseline in Fasting Insulin | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting insulin as covariates. |
| Change From Baseline in Proinsulin/Insulin Ratio | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin/insulin ratio as covariates. |
| Change From Baseline in C-peptide | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | 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, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting C-peptide as covariates. |
| Change From Baseline in Calculated HOMA Insulin Resistance | Baseline and Weeks 12, 26, 42 and 52. | 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. The change from Baseline in HOMA IR was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA insulin resistance as covariates. |
| Change From Baseline in Calculated HOMA Beta-cell Function | Baseline and Weeks 12, 26, 42 and 52. | 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 The change from Baseline in the homeostasis model assessment of beta cell function was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as covariates. |
| Change From Baseline in Body Weight | Baseline and Weeks 4, 8, 12, 26, 42 and 52. | Change from Baseline in body weight was assessed at Weeks 4, 8, 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline body weight as covariates. |
| Change From Baseline in Total Cholesterol | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as covariates. |
| Change From Baseline in High-Density Lipoprotein Cholesterol | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as covariates. |
| Change From Baseline in Low-Density Lipoprotein Cholesterol | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as covariates. |
| Change From Baseline in Triglycerides | Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. | Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline triglycerides as covariates. |
| Change From Baseline in Free Fatty Acids | Baseline and Weeks 12, 26, 42, and 52. | Change from Baseline in free fatty acids was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline free fatty acids as covariates. |
| Change From Baseline in Apolipoprotein A1 | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as covariates. |
| Change From Baseline in Apolipoprotein A2 | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as covariates. |
| Change From Baseline in Apolipoprotein B | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in Apolipoprotein B was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as covariates. |
| Change From Baseline in Apolipoprotein C-III | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in Apolipoprotein C-III was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as covariates. |
| Change From Baseline in Plasminogen Activator Inhibitor-1 | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as covariates. |
| Change From Baseline in High-sensitivity C-Reactive Protein | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline hsCRP as covariates. |
| Change From Baseline in Adiponectin | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in adiponectin was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline adiponectin as covariates. |
| Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Baseline and Weeks 12, 26, 42 and 52. | Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline NMR triglycerides as covariates. |
| Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Baseline and Weeks 12, 26, 42 and 52. | 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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron particles as covariates. |
| Change From Baseline in Low Density Lipoprotein (LDL) Particles | Baseline and Weeks 12, 26, 42 and 52. | 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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL particles as covariates. |
| Change From Baseline in VLDL / Chylomicron Triglycerides | Baseline and Weeks 12, 26, 42 and 52. | The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron triglycerides as covariates. |
| Change From Baseline in VLDL Particles | Baseline and Weeks 12, 26, 42 and 52. | The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL particles as covariates. |
| Change From Baseline in HbA1c Over Time | Baseline and Weeks 4, 8, 12, 16, 20, 34 and 42. | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and baseline metformin dose and baseline HbA1c as covariates. |
| Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Baseline and Weeks 12, 26, 42 and 52. | The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline IDL particles as covariates. |
| Change From Baseline in Mean LDL Particle Size | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as covariates. |
| Change From Baseline in High Density Lipoprotein (HDL) Particles | Baseline and Weeks 12, 26, 42 and 52. | The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL particles as covariates. |
| Change From Baseline in Mean HDL Particle Size | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as covariates. |
| Change From Baseline in Mean VLDL Particle Size | Baseline and Weeks 12, 26, 42 and 52. | Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as covariates. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 235 investigative sites in 16 countries worldwide from 30 January 2007 to 5 June 2009.
Pre-assignment details
Participants with a diagnosis of type 2 diabetes who were experiencing inadequate glycemic control on their existing treatment regimen of metformin HCl plus pioglitazone were randomized in a 1:1 ratio to 1 of 2 treatment arms: addition of alogliptin 25 mg versus titration of pioglitazone 30 mg to 45 mg.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin Alogliptin 25 mg, tablets, orally, once daily; pioglitazone 30 mg, tablets, orally, once daily; and the maximum tolerated dose of metformin, tablets, orally, for up to 52 weeks. | 404 |
| Pioglitazone 45 mg + Metformin Alogliptin placebo-matching tablets, orally, once daily; pioglitazone 45 mg, tablets, orally, once daily; and the maximum tolerated dose of metformin, tablets, orally, for up to 52 weeks. | 399 |
| Total | 803 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 16 |
| Overall Study | Hyperglycemic Rescue | 44 | 87 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Other | 2 | 3 |
| Overall Study | Physician Decision | 6 | 8 |
| Overall Study | Protocol Violation | 25 | 20 |
| Overall Study | Withdrawal by Subject | 25 | 20 |
Baseline characteristics
| Characteristic | Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Pioglitazone 45 mg + Metformin | Total |
|---|---|---|---|
| Age Continuous | 54.3 years STANDARD_DEVIATION 9.86 | 55.9 years STANDARD_DEVIATION 9.94 | 55.1 years STANDARD_DEVIATION 9.93 |
| Age, Customized <65 years | 339 participants | 320 participants | 659 participants |
| Age, Customized ≥65 years | 65 participants | 79 participants | 144 participants |
| Baseline daily metformin HCl use | 1700.0 mg | 1700.0 mg | 1700.0 mg |
| BMI | 31.52 kg/m^2 STANDARD_DEVIATION 5.248 | 31.58 kg/m^2 STANDARD_DEVIATION 5.177 | 31.55 kg/m^2 STANDARD_DEVIATION 5.21 |
| Current smoker No | 304 participants | 300 participants | 604 participants |
| Current smoker Yes | 100 participants | 99 participants | 199 participants |
| Duration of diabetes | 7.47 years STANDARD_DEVIATION 5.243 | 6.85 years STANDARD_DEVIATION 4.611 | 7.16 years STANDARD_DEVIATION 4.946 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 31 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 374 Participants | 368 Participants | 742 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c <8.0% | 161 participants | 163 participants | 324 participants |
| HbA1c ≥8.0% | 243 participants | 236 participants | 479 participants |
| Height | 166.82 cm STANDARD_DEVIATION 9.884 | 166.37 cm STANDARD_DEVIATION 10.856 | 166.60 cm STANDARD_DEVIATION 10.375 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 79 participants | 78 participants | 157 participants |
| Race/Ethnicity, Customized Black or African American | 41 participants | 36 participants | 77 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Other | 38 participants | 29 participants | 67 participants |
| Race/Ethnicity, Customized White | 242 participants | 256 participants | 498 participants |
| Sex: Female, Male Female | 194 Participants | 195 Participants | 389 Participants |
| Sex: Female, Male Male | 210 Participants | 204 Participants | 414 Participants |
| Weight | 88.16 kg STANDARD_DEVIATION 18.898 | 87.98 kg STANDARD_DEVIATION 19.283 | 88.07 kg STANDARD_DEVIATION 19.078 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 116 / 404 | 104 / 399 |
| serious Total, serious adverse events | 20 / 404 | 20 / 399 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
The change from Baseline to Week 26 and Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Time frame: Baseline and Weeks 26 and 52.
Population: Per-protocol set included all randomized patients who received at least 1 dose of double-blind study medication and who had no major protocol violations. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change from Baseline at Week 26 | -0.89 percentage of glycosylated hemoglobin | Standard Error 0.042 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change from Baseline at Week 52 | -0.70 percentage of glycosylated hemoglobin | Standard Error 0.048 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change from Baseline at Week 26 | -0.42 percentage of glycosylated hemoglobin | Standard Error 0.042 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change from Baseline at Week 52 | -0.29 percentage of glycosylated hemoglobin | Standard Error 0.048 |
Comparison: The analysis was conducted at the 1-sided 0.025 significance level. Non-inferiority was demonstrated if the upper confidence limit for the LS mean difference was less than +0.3%.ANCOVA
Comparison: Comparison of Change from Baseline at Week 52. The null hypothesis was that the average change from Baseline in HbA1c at Week 52 for the alogliptin 25 mg addition group is inferior to the average change for the pioglitazone titration group. The alternative hypothesis was that the change from Baseline in HbA1c for the alogliptin 25 mg addition group was non-inferior to the change for the pioglitazone titration group for at Week 52.ANCOVA
Secondary
Change From Baseline in Adiponectin
Change from Baseline in adiponectin was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline adiponectin as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Adiponectin | Week 12 (n=355, 361) | 1.15 μg/mL | Standard Error 0.453 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Adiponectin | Week 26 (n=366, 371) | 1.17 μg/mL | Standard Error 0.599 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Adiponectin | Week 42 (n=367, 371) | -0.41 μg/mL | Standard Error 0.529 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Adiponectin | Week 52 (n=367, 371) | -0.70 μg/mL | Standard Error 0.595 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Adiponectin | Week 52 (n=367, 371) | 2.21 μg/mL | Standard Error 0.591 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Adiponectin | Week 12 (n=355, 361) | 2.97 μg/mL | Standard Error 0.449 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Adiponectin | Week 42 (n=367, 371) | 3.04 μg/mL | Standard Error 0.526 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Adiponectin | Week 26 (n=366, 371) | 4.19 μg/mL | Standard Error 0.595 |
Comparison: Comparison of change from Baseline at Week 52.p-value: <0.00195% CI: [-4.57, -1.27]ANCOVA
Secondary
Change From Baseline in Apolipoprotein A1
Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 12 (n=348, 355) | 0.5 mg/dL | Standard Error 0.99 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 26 (n=359, 363) | 0.1 mg/dL | Standard Error 0.95 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 42 (n=360, 363) | -2.1 mg/dL | Standard Error 0.95 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 52 (n=360, 363) | -4.5 mg/dL | Standard Error 0.99 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 52 (n=360, 363) | -4.4 mg/dL | Standard Error 0.98 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 12 (n=348, 355) | 0.0 mg/dL | Standard Error 0.98 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 42 (n=360, 363) | -2.2 mg/dL | Standard Error 0.95 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A1 | Week 26 (n=359, 363) | -0.9 mg/dL | Standard Error 0.95 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.93495% CI: [-2.9, 2.6]ANCOVA
Secondary
Change From Baseline in Apolipoprotein A2
Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 12 (n=348, 355) | -0.4 mg/dL | Standard Error 0.22 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 26 (n=359, 363) | 0.4 mg/dL | Standard Error 0.23 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 42 (n=360, 363) | 0.8 mg/dL | Standard Error 0.25 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 52 (n=360, 363) | 0.3 mg/dL | Standard Error 0.24 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 52 (n=360, 363) | 1.0 mg/dL | Standard Error 0.24 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 12 (n=348, 355) | 0.6 mg/dL | Standard Error 0.22 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 42 (n=360, 363) | 1.1 mg/dL | Standard Error 0.25 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein A2 | Week 26 (n=359, 363) | 0.7 mg/dL | Standard Error 0.22 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.0795% CI: [-1.3, 0.1]ANCOVA
Secondary
Change From Baseline in Apolipoprotein B
Change from Baseline in Apolipoprotein B was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: Full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 12 [N=348, 355] | -3.1 mg/dL | Standard Error 1.02 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 26 [N=359, 363] | -0.6 mg/dL | Standard Error 1.09 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 42 [N=360, 363] | -0.4 mg/dL | Standard Error 1.15 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 52 [N=360, 363] | -1.2 mg/dL | Standard Error 1.1 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 52 [N=360, 363] | 1.7 mg/dL | Standard Error 1.1 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 12 [N=348, 355] | 0.1 mg/dL | Standard Error 1.01 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 42 [N=360, 363] | 1.8 mg/dL | Standard Error 1.15 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein B | Week 26 [N=359, 363] | 1.1 mg/dL | Standard Error 1.08 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.06495% CI: [-5.9, 0.2]ANCOVA
Secondary
Change From Baseline in Apolipoprotein C-III
Change from Baseline in Apolipoprotein C-III was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: Full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 12 (n=352, 361) | -0.6 mg/dL | Standard Error 0.15 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 26 (n=365, 369) | -0.1 mg/dL | Standard Error 0.17 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 42 (n=366, 369) | -0.3 mg/dL | Standard Error 0.17 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 52 (n=366, 369) | -0.5 mg/dL | Standard Error 0.16 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 52 (n=366, 369) | 0.0 mg/dL | Standard Error 0.16 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 12 (n=352, 361) | 0.1 mg/dL | Standard Error 0.15 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 42 (n=366, 369) | 0.2 mg/dL | Standard Error 0.17 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Apolipoprotein C-III | Week 26 (n=365, 369) | 0.2 mg/dL | Standard Error 0.17 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.02295% CI: [-1, -0.1]ANCOVA
Secondary
Change From Baseline in Body Weight
Change from Baseline in body weight was assessed at Weeks 4, 8, 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline body weight as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 4 (n=354, 344) | 0.18 kg | Standard Error 0.094 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 8 (n=394, 394 | 0.31 kg | Standard Error 0.107 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 12 (n=395, 394) | 0.35 kg | Standard Error 0.124 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 26 (n=395, 394) | 0.73 kg | Standard Error 0.15 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 42 (n=395, 394) | 1.09 kg | Standard Error 0.179 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Body Weight | Week 52 (n=395, 394) | 1.10 kg | Standard Error 0.194 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 42 (n=395, 394) | 1.52 kg | Standard Error 0.179 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 4 (n=354, 344) | 0.32 kg | Standard Error 0.095 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 26 (n=395, 394) | 0.97 kg | Standard Error 0.15 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 8 (n=394, 394 | 0.51 kg | Standard Error 0.107 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 52 (n=395, 394) | 1.60 kg | Standard Error 0.194 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Body Weight | Week 12 (n=395, 394) | 0.64 kg | Standard Error 0.124 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.07195% CI: [-1.03, 0.04]ANCOVA
Secondary
Change From Baseline 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 The change from Baseline in the homeostasis model assessment of beta cell function was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 12 (n=380, 377) | 14.770 percentage beta cell function | Standard Error 3.6543 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 26 (n=381, 377) | 30.012 percentage beta cell function | Standard Error 8.6151 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 42 (n=381, 377) | 15.397 percentage beta cell function | Standard Error 2.7628 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 52 (n=381, 377) | 15.020 percentage beta cell function | Standard Error 2.7396 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 52 (n=381, 377) | 2.057 percentage beta cell function | Standard Error 2.7541 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 12 (n=380, 377) | 4.580 percentage beta cell function | Standard Error 3.6689 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 42 (n=381, 377) | 2.400 percentage beta cell function | Standard Error 2.7774 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Beta-cell Function | Week 26 (n=381, 377) | 3.242 percentage beta cell function | Standard Error 8.6608 |
Comparison: Comparison of change from Baseline at Week 52.p-value: <0.00195% CI: [5.333, 20.592]ANCOVA
Secondary
Change From Baseline 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. The change from Baseline in HOMA IR was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA insulin resistance as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 12 (n=380, 378) | 0.007 insulin resistance | Standard Error 0.2339 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 26 (n=381, 378) | 0.336 insulin resistance | Standard Error 0.2446 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 42 (n=381, 378) | 0.200 insulin resistance | Standard Error 0.2103 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 52 (n=381, 378) | 0.353 insulin resistance | Standard Error 0.231 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 52 (n=381, 378) | 0.541 insulin resistance | Standard Error 0.2319 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 12 (n=380, 378) | 0.350 insulin resistance | Standard Error 0.2345 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 42 (n=381, 378) | 0.431 insulin resistance | Standard Error 0.2111 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Calculated HOMA Insulin Resistance | Week 26 (n=381, 378) | 0.312 insulin resistance | Standard Error 0.2455 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.56795% CI: [-0.83, 0.455]ANCOVA
Secondary
Change From Baseline in C-peptide
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, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting C-peptide as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 52 (n=395, 390) | 0.182 ng/mL | Standard Error 0.043 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 4 (n=349, 333) | 0.110 ng/mL | Standard Error 0.035 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 8 (n=393, 389) | 0.074 ng/mL | Standard Error 0.0387 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 12 (n=394, 390) | 0.070 ng/mL | Standard Error 0.0459 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 16 (n=395, 390) | 0.064 ng/mL | Standard Error 0.038 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 20 (n=395, 390) | 0.104 ng/mL | Standard Error 0.0384 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 26 (n=395, 390) | 0.102 ng/mL | Standard Error 0.0407 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 34 (n=395, 390) | 0.118 ng/mL | Standard Error 0.0403 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in C-peptide | Week 42 (n=395, 390) | 0.140 ng/mL | Standard Error 0.0413 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 34 (n=395, 390) | 0.003 ng/mL | Standard Error 0.0406 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 20 (n=395, 390) | -0.001 ng/mL | Standard Error 0.0386 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 4 (n=349, 333) | -0.033 ng/mL | Standard Error 0.0358 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 52 (n=395, 390) | 0.108 ng/mL | Standard Error 0.0433 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 8 (n=393, 389) | -0.038 ng/mL | Standard Error 0.0389 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 26 (n=395, 390) | -0.013 ng/mL | Standard Error 0.0409 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 12 (n=394, 390) | 0.030 ng/mL | Standard Error 0.0462 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 42 (n=395, 390) | 0.037 ng/mL | Standard Error 0.0415 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in C-peptide | Week 16 (n=395, 390) | 0.010 ng/mL | Standard Error 0.0382 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.2395% CI: [-0.047, 0.193]ANCOVA
Secondary
Change From Baseline in Fasting Insulin
The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting insulin as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 8 (n=382, 378) | 0.72 μIU/mL | Standard Error 0.393 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 26 (n=383, 378) | 1.94 μIU/mL | Standard Error 0.479 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 16 (n=383, 378) | 1.19 μIU/mL | Standard Error 0.414 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 34 (n=383, 378) | 1.41 μIU/mL | Standard Error 0.43 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 12 (n=382, 378) | 1.21 μIU/mL | Standard Error 0.505 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 42 (n=383, 378) | 1.79 μIU/mL | Standard Error 0.441 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 20 (n=383, 378) | 1.60 μIU/mL | Standard Error 0.414 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 52 (n=383, 378) | 1.91 μIU/mL | Standard Error 0.47 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Insulin | Week 4 (n=344, 328) | 0.53 μIU/mL | Standard Error 0.346 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 52 (n=383, 378) | 1.18 μIU/mL | Standard Error 0.473 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 4 (n=344, 328) | -0.54 μIU/mL | Standard Error 0.355 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 8 (n=382, 378) | 0.05 μIU/mL | Standard Error 0.395 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 12 (n=382, 378) | 1.22 μIU/mL | Standard Error 0.507 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 16 (n=383, 378) | 0.56 μIU/mL | Standard Error 0.416 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 20 (n=383, 378) | 0.38 μIU/mL | Standard Error 0.417 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 26 (n=383, 378) | 0.88 μIU/mL | Standard Error 0.482 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 34 (n=383, 378) | 0.83 μIU/mL | Standard Error 0.433 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Insulin | Week 42 (n=383, 378) | 1.10 μIU/mL | Standard Error 0.443 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.27695% CI: [-0.58, 2.04]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose
The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline FPG as covariates.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set, which included all randomized patients who received at least 1 dose of double-blind study drug and where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=360, 345) | -15.5 mg/dL | Standard Error 1.56 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=397, 394) | -17.7 mg/dL | Standard Error 1.48 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=399, 396) | -19.1 mg/dL | Standard Error 1.56 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=399, 396) | -19.6 mg/dL | Standard Error 1.6 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=399, 396) | -18.0 mg/dL | Standard Error 1.6 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=399, 396) | -16.4 mg/dL | Standard Error 1.65 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=399, 396) | -17.1 mg/dL | Standard Error 1.79 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 34 (n=399, 396) | -13.6 mg/dL | Standard Error 1.88 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 42 (n=399, 396) | -15.9 mg/dL | Standard Error 1.87 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=399, 396) | -14.6 mg/dL | Standard Error 1.89 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 34 (n=399, 396) | -6.2 mg/dL | Standard Error 1.88 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=360, 345) | -0.5 mg/dL | Standard Error 1.59 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=399, 396) | -5.8 mg/dL | Standard Error 1.66 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=397, 394) | -1.4 mg/dL | Standard Error 1.49 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=399, 396) | -3.7 mg/dL | Standard Error 1.89 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=399, 396) | -5.7 mg/dL | Standard Error 1.57 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=399, 396) | -4.9 mg/dL | Standard Error 1.79 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=399, 396) | -4.8 mg/dL | Standard Error 1.61 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 42 (n=399, 396) | -4.9 mg/dL | Standard Error 1.88 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=399, 396) | -4.5 mg/dL | Standard Error 1.6 |
Comparison: Comparison of change from Baseline at Week 52.p-value: <0.00195% CI: [-16.2, -5.7]ANCOVA
Secondary
Change From Baseline in Fasting Proinsulin
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, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 8 (n=380, 376) | -2.3 pmol/L | Standard Error 0.77 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 26 (n=381, 376) | 0.6 pmol/L | Standard Error 0.82 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 16 (n=381, 376) | -0.2 pmol/L | Standard Error 1.01 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 34 (n=381, 376) | 0.9 pmol/L | Standard Error 0.86 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 12 (n=380, 376) | -1.3 pmol/L | Standard Error 0.89 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 42 (n=381, 376) | -0.1 pmol/L | Standard Error 0.8 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 20 (n=381, 376) | -0.5 pmol/L | Standard Error 0.67 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 52 (n=381, 376) | -0.5 pmol/L | Standard Error 0.74 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 4 (n=342, 325) | -2.0 pmol/L | Standard Error 0.67 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 52 (n=381, 376) | 1.2 pmol/L | Standard Error 0.74 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 4 (n=342, 325) | -0.8 pmol/L | Standard Error 0.69 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 8 (n=380, 376) | -0.5 pmol/L | Standard Error 0.77 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 12 (n=380, 376) | 1.6 pmol/L | Standard Error 0.89 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 16 (n=381, 376) | 0.6 pmol/L | Standard Error 1.02 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 20 (n=381, 376) | 0.3 pmol/L | Standard Error 0.68 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 26 (n=381, 376) | 0.7 pmol/L | Standard Error 0.83 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 34 (n=381, 376) | 0.3 pmol/L | Standard Error 0.86 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Fasting Proinsulin | Week 42 (n=381, 376) | 1.1 pmol/L | Standard Error 0.81 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.11695% CI: [-3.7, 0.4]ANCOVA
Secondary
Change From Baseline in Free Fatty Acids
Change from Baseline in free fatty acids was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline free fatty acids as covariates.
Time frame: Baseline and Weeks 12, 26, 42, and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 12 (n=355, 360) | -0.0526 mmol/L | Standard Error 0.01037 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 26 (n=366, 368) | -0.0364 mmol/L | Standard Error 0.01231 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 42 (n=367, 368) | -0.0243 mmol/L | Standard Error 0.01083 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 52 (n=367, 368) | -0.0294 mmol/L | Standard Error 0.01173 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 52 (n=367, 368) | 0.0019 mmol/L | Standard Error 0.01171 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 12 (n=355, 360) | -0.0332 mmol/L | Standard Error 0.01031 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 42 (n=367, 368) | -0.0222 mmol/L | Standard Error 0.01081 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Free Fatty Acids | Week 26 (n=366, 368) | -0.0162 mmol/L | Standard Error 0.01228 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.05995% CI: [-0.064, 0.0012]ANCOVA
Secondary
Change From Baseline in HbA1c Over Time
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and baseline metformin dose and baseline HbA1c as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 34 and 42.
Population: Per-protocol set. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 12 (n=303, 306) | -0.85 percentage of glycosylated hemoglobin | Standard Error 0.037 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 20 (n=303, 306) | -0.91 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 8 (n=303, 306) | -0.71 percentage of glycosylated hemoglobin | Standard Error 0.03 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 34 (n=303, 306) | -0.82 percentage of glycosylated hemoglobin | Standard Error 0.046 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 16 (n=303, 306) | -0.91 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 42 (n=303, 306) | -0.80 percentage of glycosylated hemoglobin | Standard Error 0.048 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 4 (n=276, 277) | -0.42 percentage of glycosylated hemoglobin | Standard Error 0.025 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 42 (n=303, 306) | -0.36 percentage of glycosylated hemoglobin | Standard Error 0.048 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 4 (n=276, 277) | -0.15 percentage of glycosylated hemoglobin | Standard Error 0.025 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 8 (n=303, 306) | -0.27 percentage of glycosylated hemoglobin | Standard Error 0.03 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 12 (n=303, 306) | -0.35 percentage of glycosylated hemoglobin | Standard Error 0.037 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 16 (n=303, 306) | -0.43 percentage of glycosylated hemoglobin | Standard Error 0.038 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 20 (n=303, 306) | -0.45 percentage of glycosylated hemoglobin | Standard Error 0.039 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in HbA1c Over Time | Change from Baseline at Week 34 (n=303, 306) | -0.37 percentage of glycosylated hemoglobin | Standard Error 0.045 |
Comparison: Comparison of change from Baseline in HbA1c at Week 42.p-value: <0.00195% CI: [-0.57, -0.31]ANCOVA
Secondary
Change From Baseline in High-Density Lipoprotein Cholesterol
Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=399, 395) | -0.8 mg/dL | Standard Error 0.35 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=399, 395) | 0.0 mg/dL | Standard Error 0.37 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=399, 395) | -0.5 mg/dL | Standard Error 0.37 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 34 (n=399, 395) | -0.6 mg/dL | Standard Error 0.38 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=399, 395) | -0.2 mg/dL | Standard Error 0.42 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 42 (n=399, 395) | -0.3 mg/dL | Standard Error 0.38 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=399, 395) | -0.2 mg/dL | Standard Error 0.37 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 52 (n=395, 395) | -0.3 mg/dL | Standard Error 0.37 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=397, 392) | -0.7 mg/dL | Standard Error 0.33 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 52 (n=395, 395) | 0.3 mg/dL | Standard Error 0.37 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=397, 392) | 0.4 mg/dL | Standard Error 0.34 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=399, 395) | 0.6 mg/dL | Standard Error 0.35 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=399, 395) | 1.1 mg/dL | Standard Error 0.42 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=399, 395) | 0.9 mg/dL | Standard Error 0.38 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=399, 395) | 0.7 mg/dL | Standard Error 0.37 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=399, 395) | 0.6 mg/dL | Standard Error 0.37 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 34 (n=399, 395) | 0.3 mg/dL | Standard Error 0.38 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 42 (n=399, 395) | 0.6 mg/dL | Standard Error 0.38 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.22895% CI: [-1.7, 0.4]ANCOVA
Secondary
Change From Baseline in High Density Lipoprotein (HDL) Particles
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL particles as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=357, 361) | -0.18 μmol/L | Standard Error 0.224 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=367, 368) | 0.37 μmol/L | Standard Error 0.228 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 42 (n=367, 369) | 0.09 μmol/L | Standard Error 0.227 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 52 (n=367, 369) | 0.38 μmol/L | Standard Error 0.227 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=357, 361) | 0.08 μmol/L | Standard Error 0.102 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=367, 368) | 0.19 μmol/L | Standard Error 0.103 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 42 (n=367, 369) | 0.06 μmol/L | Standard Error 0.102 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 52 (n=367, 369) | 0.19 μmol/L | Standard Error 0.105 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=357, 361) | 0.10 μmol/L | Standard Error 0.165 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=367, 368) | 0.71 μmol/L | Standard Error 0.178 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 42 (n=367, 369) | 0.57 μmol/L | Standard Error 0.172 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 52 (n=367, 369) | 0.66 μmol/L | Standard Error 0.18 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=357, 361) | -0.38 μmol/L | Standard Error 0.243 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=367, 368) | -0.53 μmol/L | Standard Error 0.25 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 42 (n=367, 369) | -0.54 μmol/L | Standard Error 0.247 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 52 (n=367, 369) | -0.47 μmol/L | Standard Error 0.251 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 52 (n=367, 369) | -1.49 μmol/L | Standard Error 0.25 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=357, 361) | -0.14 μmol/L | Standard Error 0.223 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=357, 361) | 0.43 μmol/L | Standard Error 0.164 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=367, 368) | 0.03 μmol/L | Standard Error 0.227 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=357, 361) | -0.92 μmol/L | Standard Error 0.242 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 42 (n=367, 369) | -0.11 μmol/L | Standard Error 0.227 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=367, 368) | 0.90 μmol/L | Standard Error 0.178 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 52 (n=367, 369) | 0.02 μmol/L | Standard Error 0.226 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 42 (n=367, 369) | -1.31 μmol/L | Standard Error 0.246 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=357, 361) | 0.35 μmol/L | Standard Error 0.101 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 42 (n=367, 369) | 0.70 μmol/L | Standard Error 0.171 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=367, 368) | 0.53 μmol/L | Standard Error 0.103 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=367, 368) | -1.39 μmol/L | Standard Error 0.25 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 42 (n=367, 369) | 0.51 μmol/L | Standard Error 0.101 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 52 (n=367, 369) | 0.96 μmol/L | Standard Error 0.179 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 52 (n=367, 369) | 0.57 μmol/L | Standard Error 0.105 |
Secondary
Change From Baseline in High-sensitivity C-Reactive Protein
Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline hsCRP as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=357, 366) | 0.2989 mg/L | Standard Error 0.53213 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=366, 373) | -0.0632 mg/L | Standard Error 0.49229 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 42 (n=367, 373) | 0.7251 mg/L | Standard Error 0.48203 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 52 (n=367, 373) | 0.5875 mg/L | Standard Error 0.54194 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 52 (n=367, 373) | 1.4085 mg/L | Standard Error 0.53755 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=357, 366) | 0.7049 mg/L | Standard Error 0.52569 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 42 (n=367, 373) | 0.6443 mg/L | Standard Error 0.47813 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=366, 373) | 0.9706 mg/L | Standard Error 0.48763 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.28395% CI: [-2.3209, 0.679]ANCOVA
Secondary
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline IDL particles as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=357, 361) | -4.9 nmol/L | Standard Error 2.24 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=367, 368) | -4.1 nmol/L | Standard Error 2.39 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 42 (n=367, 369) | -5.6 nmol/L | Standard Error 2.26 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 52 (n=367, 369) | -4.5 nmol/L | Standard Error 2.22 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 52 (n=367, 369) | 3.2 nmol/L | Standard Error 2.21 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=357, 361) | 3.2 nmol/L | Standard Error 2.23 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 42 (n=367, 369) | 2.0 nmol/L | Standard Error 2.26 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=367, 368) | 1.0 nmol/L | Standard Error 2.39 |
Secondary
Change From Baseline in Low-Density Lipoprotein Cholesterol
Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=390, 386) | -0.6 mg/dL | Standard Error 1.18 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=390, 386) | -0.6 mg/dL | Standard Error 1.36 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=390, 386) | -1.7 mg/dL | Standard Error 1.31 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 34 (n=390, 386) | -1.9 mg/dL | Standard Error 1.33 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=390, 386) | -1.2 mg/dL | Standard Error 1.21 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 42 (n=390, 386) | -1.6 mg/dL | Standard Error 1.35 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=390, 386) | -2.0 mg/dL | Standard Error 1.24 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 52 (n=390, 386) | -1.9 mg/dL | Standard Error 1.32 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=388, 383) | -2.4 mg/dL | Standard Error 1.11 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 52 (n=390, 386) | 1.0 mg/dL | Standard Error 1.33 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=388, 383) | 0.0 mg/dL | Standard Error 1.12 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=390, 386) | 2.1 mg/dL | Standard Error 1.19 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=390, 386) | 1.4 mg/dL | Standard Error 1.22 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=390, 386) | -0.1 mg/dL | Standard Error 1.32 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=390, 386) | 0.1 mg/dL | Standard Error 1.25 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=390, 386) | 1.6 mg/dL | Standard Error 1.37 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 34 (n=390, 386) | 1.2 mg/dL | Standard Error 1.33 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 42 (n=390, 386) | 0.7 mg/dL | Standard Error 1.36 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.13295% CI: [-6.5, 0.9]ANCOVA
Secondary
Change From Baseline in Low Density Lipoprotein (LDL) Particles
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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL particles as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=357, 361) | -46.9 nmol/L | Standard Error 14.88 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=367, 368) | -14.0 nmol/L | Standard Error 15.83 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 42 (n=367, 369) | -11.7 nmol/L | Standard Error 16.86 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 52 (n=367, 369) | -13.0 nmol/L | Standard Error 15.98 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=357, 361) | -4.4 nmol/L | Standard Error 9.29 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=367, 368) | 1.1 nmol/L | Standard Error 10.37 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 42 (n=367, 369) | -20.8 nmol/L | Standard Error 9.68 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 52 (n=367, 369) | -19.2 nmol/L | Standard Error 10.03 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 12 (n=357, 361) | -7.0 nmol/L | Standard Error 3.45 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 26 (n=367, 368) | -0.7 nmol/L | Standard Error 3.57 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 42 (n=367, 369) | 4.1 nmol/L | Standard Error 3.82 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 52 (n=367, 369) | 2.4 nmol/L | Standard Error 3.54 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 12 (n=357, 361) | -37.6 nmol/L | Standard Error 16.93 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 26 (n=367, 368) | -10.9 nmol/L | Standard Error 17.8 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 42 (n=367, 369) | 15.0 nmol/L | Standard Error 18.63 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 52 (n=367, 369) | 10.9 nmol/L | Standard Error 17.84 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 12 (n=357, 361) | -30.6 nmol/L | Standard Error 13.84 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 26 (n=367, 368) | -10.1 nmol/L | Standard Error 14.49 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 42 (n=367, 369) | 11.0 nmol/L | Standard Error 15.13 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 52 (n=367, 369) | 8.6 nmol/L | Standard Error 14.56 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 26 (n=367, 368) | -17.5 nmol/L | Standard Error 14.47 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=357, 361) | -22.3 nmol/L | Standard Error 14.81 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 42 (n=367, 369) | 1.8 nmol/L | Standard Error 3.81 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=367, 368) | -8.2 nmol/L | Standard Error 15.81 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 52 (n=367, 369) | -3.5 nmol/L | Standard Error 17.79 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 42 (n=367, 369) | -10.7 nmol/L | Standard Error 16.81 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 52 (n=367, 369) | 1.2 nmol/L | Standard Error 3.53 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 52 (n=367, 369) | -2.7 nmol/L | Standard Error 15.94 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 52 (n=367, 369) | -4.8 nmol/L | Standard Error 14.52 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=357, 361) | -5.0 nmol/L | Standard Error 9.24 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 12 (n=357, 361) | -20.8 nmol/L | Standard Error 16.84 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=367, 368) | 8.8 nmol/L | Standard Error 10.36 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 12 (n=357, 361) | -20.6 nmol/L | Standard Error 13.77 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 42 (n=367, 369) | 0.0 nmol/L | Standard Error 9.65 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 26 (n=367, 368) | -18.2 nmol/L | Standard Error 17.77 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 52 (n=367, 369) | -2.4 nmol/L | Standard Error 10 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small Particles - Week 42 (n=367, 369) | -14.9 nmol/L | Standard Error 15.09 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 12 (n=357, 361) | -0.3 nmol/L | Standard Error 3.43 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small Particles - Week 42 (n=367, 369) | -13.0 nmol/L | Standard Error 18.58 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-small Particles - Week 26 (n=367, 368) | -0.7 nmol/L | Standard Error 3.57 |
Secondary
Change From Baseline in Mean HDL Particle Size
Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 12 (n=357, 361) | 0.04 nm | Standard Error 0.012 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 42 (n=367, 369) | 0.02 nm | Standard Error 0.012 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 26 (n=367, 368) | 0.04 nm | Standard Error 0.012 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 52 (n=367, 369) | 0.03 nm | Standard Error 0.012 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 26 (n=367, 368) | 0.07 nm | Standard Error 0.012 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 12 (n=357, 361) | 0.05 nm | Standard Error 0.012 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 52 (n=367, 369) | 0.08 nm | Standard Error 0.012 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean HDL Particle Size | Week 42 (n=367, 369) | 0.07 nm | Standard Error 0.012 |
Secondary
Change From Baseline in Mean LDL Particle Size
Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 12 (n=357, 361) | 0.05 nm | Standard Error 0.031 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 26 (n=367, 368) | 0.03 nm | Standard Error 0.032 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 42 (n=367, 369) | -0.02 nm | Standard Error 0.032 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 52 (n=367, 369) | -0.04 nm | Standard Error 0.032 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 52 (n=367, 369) | 0.03 nm | Standard Error 0.032 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 12 (n=357, 361) | 0.06 nm | Standard Error 0.031 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 42 (n=367, 369) | 0.05 nm | Standard Error 0.032 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean LDL Particle Size | Week 26 (n=367, 368) | 0.07 nm | Standard Error 0.032 |
Secondary
Change From Baseline in Mean VLDL Particle Size
Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=355, 361) | -0.67 nm | Standard Error 0.369 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=365, 368) | 0.11 nm | Standard Error 0.391 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 42 (n=365, 369) | 0.44 nm | Standard Error 0.445 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 52 (n=365, 369) | -0.12 nm | Standard Error 0.395 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 52 (n=365, 369) | -1.04 nm | Standard Error 0.393 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=355, 361) | -0.79 nm | Standard Error 0.366 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 42 (n=365, 369) | -0.79 nm | Standard Error 0.442 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=365, 368) | -0.87 nm | Standard Error 0.389 |
Secondary
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides
Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline NMR triglycerides as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=357, 361) | -8.7 mg/dL | Standard Error 3.24 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=367, 368) | -1.7 mg/dL | Standard Error 3.58 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 42 (n=367, 369) | -6.4 mg/dL | Standard Error 3.6 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 52 (n=367, 369) | -6.9 mg/dL | Standard Error 3.35 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 52 (n=367, 369) | -0.7 mg/dL | Standard Error 3.34 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=357, 361) | 0.2 mg/dL | Standard Error 3.23 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 42 (n=367, 369) | 0.7 mg/dL | Standard Error 3.59 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=367, 368) | 0.8 mg/dL | Standard Error 3.58 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.19795% CI: [-15.4, 3.2]ANCOVA
Secondary
Change From Baseline in Plasminogen Activator Inhibitor-1
Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=322, 330) | -3.23 ng/ml | Standard Error 1.483 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=342, 343) | -2.83 ng/ml | Standard Error 1.523 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 42 (n=346, 344) | -2.08 ng/ml | Standard Error 1.429 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 52 (n=346, 344) | -2.92 ng/ml | Standard Error 1.234 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 52 (n=346, 344) | -4.70 ng/ml | Standard Error 1.237 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=322, 330) | -3.59 ng/ml | Standard Error 1.464 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 42 (n=346, 344) | -4.89 ng/ml | Standard Error 1.434 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=342, 343) | -3.63 ng/ml | Standard Error 1.52 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.30895% CI: [-1.65, 5.22]ANCOVA
Secondary
Change From Baseline in Proinsulin/Insulin Ratio
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin/insulin ratio as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=380, 375) | -0.049 ratio | Standard Error 0.0148 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=381, 375) | -0.036 ratio | Standard Error 0.0081 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=381, 375) | -0.044 ratio | Standard Error 0.01 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 34 (n=381, 375) | -0.038 ratio | Standard Error 0.0084 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=380, 375) | -0.053 ratio | Standard Error 0.0105 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 42 (n=381, 375) | -0.047 ratio | Standard Error 0.0083 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=381, 375) | -0.037 ratio | Standard Error 0.0085 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 52 (n=381, 375) | -0.048 ratio | Standard Error 0.008 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=341, 325) | -0.046 ratio | Standard Error 0.0095 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 52 (n=381, 375) | -0.007 ratio | Standard Error 0.0081 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=341, 325) | -0.005 ratio | Standard Error 0.0097 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=380, 375) | -0.001 ratio | Standard Error 0.0149 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=380, 375) | 0.004 ratio | Standard Error 0.0106 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=381, 375) | 0.002 ratio | Standard Error 0.0101 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=381, 375) | -0.004 ratio | Standard Error 0.0085 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=381, 375) | -0.015 ratio | Standard Error 0.0081 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 34 (n=381, 375) | -0.004 ratio | Standard Error 0.0085 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Proinsulin/Insulin Ratio | Week 42 (n=381, 375) | -0.010 ratio | Standard Error 0.0083 |
Comparison: Comparison of change from Baseline at Week 52.p-value: <0.00195% CI: [-0.063, -0.018]ANCOVA
Secondary
Change From Baseline in Total Cholesterol
Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 8 (n=399, 395) | -4.0 mg/dL | Standard Error 1.4 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 26 (n=399, 395) | -2.1 mg/dL | Standard Error 1.62 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 16 (n=399, 395) | -4.3 mg/dL | Standard Error 1.56 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 34 (n=399, 395) | -3.5 mg/dL | Standard Error 1.61 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 12 (n=399, 395) | -3.6 mg/dL | Standard Error 1.44 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 42 (n=399, 395) | -3.8 mg/dL | Standard Error 1.62 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 20 (n=399, 395) | -3.9 mg/dL | Standard Error 1.55 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 52 (n=399, 395) | -4.4 mg/dL | Standard Error 1.58 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Total Cholesterol | Week 4 (n=397, 393) | -5.2 mg/dL | Standard Error 1.28 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 52 (n=399, 395) | -0.1 mg/dL | Standard Error 1.59 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 4 (n=397, 393) | -1.9 mg/dL | Standard Error 1.29 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 8 (n=399, 395) | 0.3 mg/dL | Standard Error 1.4 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 12 (n=399, 395) | 1.1 mg/dL | Standard Error 1.45 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 16 (n=399, 395) | -0.4 mg/dL | Standard Error 1.57 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 20 (n=399, 395) | -0.5 mg/dL | Standard Error 1.56 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 26 (n=399, 395) | 1.0 mg/dL | Standard Error 1.63 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 34 (n=399, 395) | -0.7 mg/dL | Standard Error 1.62 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Total Cholesterol | Week 42 (n=399, 395) | 0.0 mg/dL | Standard Error 1.62 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.05895% CI: [-8.6, 0.1]ANCOVA
Secondary
Change From Baseline in Triglycerides
Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline triglycerides as covariates.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 8 (n=399, 395) | -17.9 mg/dL | Standard Error 3.61 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 26 (n=399, 395) | -11.9 mg/dL | Standard Error 3.98 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 16 (n=399, 395) | -16.3 mg/dL | Standard Error 3.36 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 34 (n=399, 395) | -7.4 mg/dL | Standard Error 3.98 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 12 (n=399, 395) | -16.1 mg/dL | Standard Error 3.69 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 42 (n=399, 395) | -14.6 mg/dL | Standard Error 3.67 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 20 (n=399, 395) | -12.7 mg/dL | Standard Error 3.68 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 52 (n=399, 395) | -16.4 mg/dL | Standard Error 3.47 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Triglycerides | Week 4 (n=397, 393) | -16.4 mg/dL | Standard Error 2.98 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 52 (n=399, 395) | -7.8 mg/dL | Standard Error 3.49 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 4 (n=397, 393) | -12.2 mg/dL | Standard Error 3 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 8 (n=399, 395) | -12.3 mg/dL | Standard Error 3.63 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 12 (n=399, 395) | -4.5 mg/dL | Standard Error 3.71 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 16 (n=399, 395) | -9.4 mg/dL | Standard Error 3.38 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 20 (n=399, 395) | -8.5 mg/dL | Standard Error 3.7 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 26 (n=399, 395) | -6.3 mg/dL | Standard Error 4 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 34 (n=399, 395) | -8.1 mg/dL | Standard Error 4 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Triglycerides | Week 42 (n=399, 395) | -7.0 mg/dL | Standard Error 3.69 |
Comparison: Comparison of change from Baseline at Week 52.p-value: 0.0895% CI: [-18.3, 1]ANCOVA
Secondary
Change From Baseline in Very Low Density Lipoprotein (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 at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron particles as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=357, 361) | -0.59 nmol/L | Standard Error 1.814 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=367, 368) | 1.27 nmol/L | Standard Error 1.94 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 42 (n=367, 369) | -1.35 nmol/L | Standard Error 1.916 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 52 (n=367, 369) | -1.20 nmol/L | Standard Error 1.89 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=357, 361) | -0.83 nmol/L | Standard Error 0.247 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=367, 368) | -0.39 nmol/L | Standard Error 0.282 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 42 (n=367, 369) | -0.72 nmol/L | Standard Error 0.277 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 52 (n=367, 369) | -0.66 nmol/L | Standard Error 0.26 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 52 (n=367, 369) | -0.46 nmol/L | Standard Error 0.26 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=357, 361) | 2.39 nmol/L | Standard Error 1.805 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=357, 361) | -0.27 nmol/L | Standard Error 0.246 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=367, 368) | 3.09 nmol/L | Standard Error 1.937 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 42 (n=367, 369) | -0.38 nmol/L | Standard Error 0.277 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 42 (n=367, 369) | 1.64 nmol/L | Standard Error 1.911 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=367, 368) | -0.32 nmol/L | Standard Error 0.281 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 52 (n=367, 369) | 3.03 nmol/L | Standard Error 1.885 |
Secondary
Change From Baseline in VLDL / Chylomicron Triglycerides
The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron triglycerides as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=357, 361) | -7.6 mg/dL | Standard Error 3.22 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=367, 368) | -1.3 mg/dL | Standard Error 3.54 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 42 (n=367, 369) | -5.4 mg/dL | Standard Error 3.6 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 52 (n=367, 369) | -6.1 mg/dL | Standard Error 3.3 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 52 (n=367, 369) | -1.5 mg/dL | Standard Error 3.29 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=357, 361) | -0.2 mg/dL | Standard Error 3.2 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 42 (n=367, 369) | 0.2 mg/dL | Standard Error 3.59 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=367, 368) | 0.2 mg/dL | Standard Error 3.54 |
Secondary
Change From Baseline in VLDL Particles
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL particles as covariates.
Time frame: Baseline and Weeks 12, 26, 42 and 52.
Population: The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=357, 361) | -0.09 nmol/L | Standard Error 1.152 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=367, 368) | 1.30 nmol/L | Standard Error 1.208 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 42 (n=367, 369) | 1.03 nmol/L | Standard Error 1.307 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 52 (n=367, 369) | 0.26 nmol/L | Standard Error 1.166 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=357, 361) | -0.04 nmol/L | Standard Error 1.077 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=367, 368) | 0.07 nmol/L | Standard Error 1.121 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 42 (n=367, 369) | -1.86 nmol/L | Standard Error 1.12 |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 52 (n=367, 369) | -1.02 nmol/L | Standard Error 1.192 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 52 (n=367, 369) | 1.58 nmol/L | Standard Error 1.189 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=357, 361) | 1.74 nmol/L | Standard Error 1.146 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=357, 361) | 1.30 nmol/L | Standard Error 1.072 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=367, 368) | 2.23 nmol/L | Standard Error 1.207 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 42 (n=367, 369) | -0.21 nmol/L | Standard Error 1.117 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 42 (n=367, 369) | 2.43 nmol/L | Standard Error 1.303 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=367, 368) | 1.47 nmol/L | Standard Error 1.119 |
| Pioglitazone 45 mg + Metformin | Change From Baseline in VLDL Particles | Medium Particles - Week 52 (n=367, 369) | 2.12 nmol/L | Standard Error 1.163 |
Secondary
Percentage of Participants Meeting Hyperglycemic Rescue Criteria
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 7 days after the first sample and analyzed by the central laboratory: 1. After more than 2 weeks of treatment but prior to the Week 4 Visit: A single fasting plasma glucose (FPG) ≥275 mg/dL; 2. From the Week 4 Visit but prior to the Week 8 Visit: A single FPG ≥250 mg/dL; 3. From the Week 8 Visit but prior to the Week 12 Visit: A single FPG ≥225 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 the baseline HbA1c.
Time frame: Baseline to Week 52
Population: Full Analysis Set including patients with a postbaseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants Meeting Hyperglycemic Rescue Criteria | 10.9 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants Meeting Hyperglycemic Rescue Criteria | 21.7 percentage of participants |
Comparison: Comparison of incidence of hyperglycemic rescue through Week 52.p-value: <0.001Extended Mantel Haenszel Test
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | Week 26 | 72.0 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | Week 52 | 60.9 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | Week 26 | 42.1 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% | Week 52 | 37.6 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0% | Week 26 | 42.3 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0% | Week 52 | 35.6 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0% | Week 26 | 20.3 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0% | Week 52 | 17.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Week 26 | 18.6 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Week 52 | 17.1 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Week 26 | 7.5 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% | Week 52 | 8.0 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% | Week 26 | 8.2 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% | Week 52 | 7.9 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% | Week 26 | 3.0 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% | Week 52 | 3.3 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Week 26 | 13.9 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Week 52 | 8.7 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Week 26 | 7.8 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% | Week 52 | 4.3 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% | Week 26 | 39.1 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% | Week 52 | 33.2 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% | Week 26 | 25.8 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% | Week 52 | 21.3 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Time frame: Weeks 26 and 52.
Population: The full analysis set. Patients who did not complete the scheduled Week 26 or Week 52 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Week 26 | 64.9 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Week 52 | 59.9 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Week 26 | 47.1 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% | Week 52 | 44.1 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: Baseline to Week 52
Population: Full Analysis Set including patients with at least one non-missing fasting plasma glucose result in each treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg + Pioglitazone 30 mg + Metformin | Percentage of Participants With Marked Hyperglycemia | 27.3 percentage of participants |
| Pioglitazone 45 mg + Metformin | Percentage of Participants With Marked Hyperglycemia | 36.1 percentage of participants |
Comparison: Comparison of incidence of marked hyperglycemia through Week 52.p-value: <0.001Extended Mantel Haenszel Test