Diabetes Mellitus
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Brief summary
The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with diet and exercise alone.
Detailed description
There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected, placing an ever-increasing burden on families and the health care system. Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha- glucosidase, analogs of glucagon-like peptide-1, and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have reaching the target glycosylated hemoglobin level less than 7%. SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. As the rate of newly diagnosed cases of type 2 diabetes mellitus continues to grow, so does the need for products that will provide better glycemic control and improved safety and tolerability. Alogliptin and pioglitazone have complementary actions. Alogliptin inhibits the degradation of glucagon-like peptide-1 by inhibiting the enzyme dipeptidyl peptidase IV, thus augmenting glucose-dependent insulin secretion while pioglitazone is a peripheral and hepatic insulin sensitizer. Given the complementary mechanisms of action of alogliptin (stimulates insulin secretion) and pioglitazone (enhances insulin sensitivity), the addition of combination therapy in treatment naïve type 2 diabetes patients may potentially allow the patients to reach and maintain their glycosylated hemoglobin goal more effectively. The aim of this study is to evaluate the effectiveness of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on diet and exercise alone. Study participation is anticipated to be approximately 8.5 months.
Interventions
DRUGAlogliptin
Alogliptin tablets.
DRUGPioglitazone
Pioglitazone tablets.
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
* Historical diagnosis of type 2 diabetes. * Failed treatment with diet and exercise for at least 2 months prior to Screening. * Is experiencing inadequate glycemic control as defined as glycosylated hemoglobin concentration between 7.5-11%, inclusive. * Has received any antidiabetic therapy for less than 7 days within 3 months prior to Screening. * Has a body mass index greater than or equal to 23 kg/m2 and less than or equal to45 kg/m2. * Fasting C-peptide greater than or equal to 0.8 ng per mL. * Regular use of other, non-excluded medications is allowed if participant is on a stable dose for at least 4 weeks prior to Screening. * 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. * Must be willing and able to monitor their blood concentrations with a home glucose monitor.
Exclusion criteria
* Systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure greater than or equal to 100 mmHg. * Hemoglobin less than or equal to 12 g per dL for males and less than or equal to 10 g per dL for females. * Alanine aminotransferase greater than or equal to 2.5times the upper limit of normal. * Serum creatinine greater than 2.0 mg per dL. * Thyroid stimulating hormone level greater than the upper limit of normal range. * Major illness or debility that in the investigator's opinion prohibits the subject from completing the study. * Urine albumin to creatinine ratio of greater than 1000 ug per mg at Screening. If elevated, the subject may be rescreened within 1 week. * 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 laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening. * History of gastroparesis. * Has New York Heart Association Class I to IV heart failure regardless of therapy. * History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 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 participant's ability to participate in the study. * History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors. * Any alteration in angiotensin-II receptor inhibitors within 2 months prior to Randomization, if applicable. * History of alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day) or substance abuse (defined as illicit drug use) within 2 years prior to Screening. * Received any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening. * Previously participated in an investigational study of SYR-322. * Glycosylated hemoglobin concentration between 7.5-11%, inclusive, and a fasting plasma glucose less than 310 mg per dL. * At least 75% compliant with the single-blind placebo regimen during the run-in/stabilization period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) | Baseline and Week 26 | The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose Over Time | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26. | The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline plasma glucose as a covariate. |
| Percentage of Participants With Marked Hyperglycemia | Weeks 1, 2, 4, 8, 12, 16, 20 and 26. | Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL. Study week windows are defined to place hyperglycemia into visit categories. |
| Percentage of Participants Meeting Rescue Criteria | Weeks 4, 8, 12, 16, 20 and 26. | Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days after the first sample and analyzed by the central laboratory: 1. After more than 4 weeks of treatment but prior to the Week 8 Visit: a single fasting plasma glucose ≥310 mg/dL (≥17.5 mmol/L); 2. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥275 mg/dL (≥15.27 mmol/L); 3. 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. |
| Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤6.5%. |
| Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7%. |
| Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% | Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 0.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1.5%. |
| Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% | Baseline and Week 26 | Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 2.0%. |
| Change From Baseline in Fasting Proinsulin | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline proinsulin as a covariate. |
| Change From Baseline in Insulin | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline insulin as a covariate. |
| Change From Baseline in Proinsulin/Insulin Ratio | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment and geographic region as class variables and Baseline proinsulin/insulin ratio as a covariate. |
| Change From Baseline in C-peptide Levels | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline C-peptide as a covariate. |
| Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Baseline and Weeks 12 and 26. | The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) \* fasting plasma glucose (mmol/L) / 22.5 A higher number indicates a greater degree of insulin resistance. The change from Baseline in HOMA IR was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA IR as a covariate. |
| Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Baseline and Weeks 12 and 26. | The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 \* insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5 The change from Baseline in the homeostasis model assessment of beta cell function was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA beta cell function as a covariate. |
| Change From Baseline in Body Weight | Baseline and Weeks 8, 12, 20 and 26. | Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline weight as a covariate. |
| Change From Baseline in Total Cholesterol Level | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in total cholesterol level was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline total cholesterol as a covariate. |
| Change From Baseline in Low-Density Lipoprotein Cholesterol | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL cholesterol as a covariate. |
| Change From Baseline in High-Density Lipoprotein Cholesterol | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL cholesterol as a covariate. |
| Change From Baseline in Triglyceride Levels | Baseline and Weeks 4, 8, 12, 16, 20 and 26. | Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline triglycerides as a covariate. |
| Change From Baseline in Free Fatty Acids | Baseline and Weeks 12 and 26. | Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline free fatty acid as a covariate. |
| Change From Baseline in Plasminogen Activator Inhibitor-1 | Baseline and Weeks 12 and 26. | Change from Baseline in plasminogen activator inhibitor-1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline plasminogen activator inhibitor-1 as a covariate. |
| Change From Baseline in High-sensitivity C-Reactive Protein | Baseline and Weeks 12 and 26. | Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline hsCRP as a covariate. |
| Change From Baseline in Adiponectin | Baseline and Weeks 12 and 26. | Change from Baseline in adiponectin was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline adiponectin as a covariate. |
| Change From Baseline in Apolipoprotein A1 | Baseline and Weeks 12 and 26. | Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline apolipoprotein A1 as a covariate. |
| Change From Baseline in Apolipoprotein A2 | Baseline and Weeks 12 and 26. | Change from Baseline in apolipoprotein A2 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein A2 as a covariate. |
| Change From Baseline in Apolipoprotein B | Baseline and Weeks 12 and 26. | Change from Baseline in apolipoprotein B was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein B as a covariate. |
| Change From Baseline in Apolipoprotein C-III | Baseline and Weeks 12 and 26. | Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein C-III as a covariate. |
| Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Baseline and Weeks 12 and 26. | Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline NMR total triglycerides as a covariate. |
| Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Baseline and Weeks 12 and 26. | The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron particles as a covariate. |
| Change From Baseline in VLDL / Chylomicron Triglycerides | Baseline and Weeks 12 and 26. | The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron triglycerides as a covariate. |
| Change From Baseline in VLDL Particles | Baseline and Weeks 12 and 26. | The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL particles as a covariate. |
| Change From Baseline in Mean VLDL Particle Size | Baseline and Weeks 12 and 26. | Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean VLDL particle size as a covariate. |
| Change From Baseline in HbA1c Over Time | Baseline and Weeks 4, 8, 12, 16 and 20. | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at 4 week intervals during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment and geographic region as class variables and baseline HbA1c as a covariate. |
| Change From Baseline in Low Density Lipoprotein (LDL) Particles | Baseline and Weeks 12 and 26. | The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL particles as a covariate. |
| Change From Baseline in Mean LDL Particle Size | Baseline and Weeks 12 and 26. | Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean LDL particle size as a covariate. |
| Change From Baseline in High Density Lipoprotein (HDL) Particles | Baseline and Weeks 12 and 26. | The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL particles as a covariate. |
| Change From Baseline in Mean HDL Particle Size | Baseline and Weeks 12 and 26. | Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean HDL particle size as a covariate. |
| Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Baseline and Weeks 12 and 26. | The change from Baseline in levels of IDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline IDL particles as a covariate. |
Countries
Argentina, Australia, Brazil, Bulgaria, Chile, Croatia, Estonia, Guatemala, Hungary, India, Israel, Latvia, Lithuania, Mexico, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at 268 investigative sites in 23 countries from 02 November 2006 to 13 February 2008.
Pre-assignment details
Participants with a diagnosis of type 2 diabetes who were inadequately controlled with diet and exercise were randomized to 1 of 4 treatment groups in a 1:1:1:1 ratio as follows: Alogliptin alone, pioglitazone alone, alogliptin 25 mg + pioglitazone 30 mg and alogliptin 12.5 mg + pioglitazone 30 mg.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. | 164 |
| Pioglitazone 30 mg Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. | 163 |
| Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. | 164 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. | 164 |
| Total | 655 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 | 6 | 6 |
| Overall Study | Hyperglycemic Rescue | 18 | 10 | 4 | 6 |
| Overall Study | Lost to Follow-up | 2 | 6 | 5 | 5 |
| Overall Study | Other | 1 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 6 | 4 | 2 | 2 |
| Overall Study | Protocol Violation | 2 | 3 | 6 | 7 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 5 | 12 |
Baseline characteristics
| Characteristic | Pioglitazone 30 mg | Total | Alogliptin 12.5 mg + Pioglitazone 30 mg | Alogliptin 25 mg | Alogliptin 25 mg + Pioglitazone 30 mg |
|---|---|---|---|---|---|
| Age Continuous | 51.5 years STANDARD_DEVIATION 10.72 | 52.6 years STANDARD_DEVIATION 10.88 | 53.5 years STANDARD_DEVIATION 11.37 | 52.6 years STANDARD_DEVIATION 10.38 | 52.8 years STANDARD_DEVIATION 11.01 |
| Age, Customized < 65 years | 143 participants | 557 participants | 130 participants | 144 participants | 140 participants |
| Age, Customized ≥ 65 years | 20 participants | 98 participants | 34 participants | 20 participants | 24 participants |
| Body Mass Index (BMI) | 30.87 kg/m^2 STANDARD_DEVIATION 4.938 | 31.13 kg/m^2 STANDARD_DEVIATION 5.382 | 30.71 kg/m^2 STANDARD_DEVIATION 5.621 | 31.61 kg/m^2 STANDARD_DEVIATION 5.587 | 31.32 kg/m^2 STANDARD_DEVIATION 5.354 |
| Duration of diabetes | 3.20 years STANDARD_DEVIATION 3.739 | 3.21 years STANDARD_DEVIATION 3.704 | 3.36 years STANDARD_DEVIATION 4.166 | 3.23 years STANDARD_DEVIATION 3.559 | 3.05 years STANDARD_DEVIATION 3.328 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 65 Participants | 248 Participants | 62 Participants | 63 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants | 407 Participants | 102 Participants | 101 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 57 Participants | 16 Participants | 14 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 38 Participants | 9 Participants | 8 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 32 Participants | 6 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) White | 130 Participants | 526 Participants | 132 Participants | 135 Participants | 129 Participants |
| Sex: Female, Male Female | 73 Participants | 335 Participants | 83 Participants | 88 Participants | 91 Participants |
| Sex: Female, Male Male | 90 Participants | 320 Participants | 81 Participants | 76 Participants | 73 Participants |
| Weight | 85.53 kg STANDARD_DEVIATION 16.254 | 85.50 kg STANDARD_DEVIATION 19.062 | 84.38 kg STANDARD_DEVIATION 20.378 | 86.72 kg STANDARD_DEVIATION 19.033 | 85.39 kg STANDARD_DEVIATION 20.374 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 164 | 25 / 163 | 37 / 164 | 24 / 163 |
| serious Total, serious adverse events | 1 / 164 | 6 / 163 | 8 / 164 | 1 / 163 |
Outcome results
Primary
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c)
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Time frame: Baseline and Week 26
Population: The Full analysis Set (all randomized patients who took at least 1 dose of double-blind study drug) where a Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alogliptin 25 mg | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) | -0.96 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Pioglitazone 30 mg | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) | -1.15 percentage of glycosylated hemoglobin | Standard Error 0.083 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) | -1.71 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) | -1.56 percentage of glycosylated hemoglobin | Standard Error 0.081 |
Comparison: The primary efficacy variable was defined as change from Baseline in HbA1c level at Week 26. The null hypothesis was that the average change from Baseline in HbA1c at Week 26 for the A25 + P30 group would be equal to the average changes for the P30 alone and A25 alone groups; further, under the null hypothesis, the average change from Baseline in HbA1c at Week 26 for the A12.5 + P30 group was equal to the average change for the P30 alone group.p-value: <0.00195% CI: [-0.78, -0.33]ANCOVA
p-value: <0.00195% CI: [-0.98, -0.53]ANCOVA
p-value: <0.00195% CI: [-0.63, -0.18]ANCOVA
Secondary
Change From Baseline in Adiponectin
Change from Baseline in adiponectin was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline adiponectin as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Adiponectin | Week 12 (n=148, 137, 141, 147) | -0.28 μg/mL | Standard Error 0.56 |
| Alogliptin 25 mg | Change From Baseline in Adiponectin | Week 26 (n=154, 137, 147, 149) | -0.09 μg/mL | Standard Error 0.57 |
| Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 26 (n=154, 137, 147, 149) | 6.90 μg/mL | Standard Error 0.605 |
| Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 12 (n=148, 137, 141, 147) | 6.35 μg/mL | Standard Error 0.582 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 12 (n=148, 137, 141, 147) | 8.10 μg/mL | Standard Error 0.575 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 26 (n=154, 137, 147, 149) | 6.85 μg/mL | Standard Error 0.586 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 12 (n=148, 137, 141, 147) | 7.50 μg/mL | Standard Error 0.562 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Adiponectin | Week 26 (n=154, 137, 147, 149) | 7.16 μg/mL | Standard Error 0.581 |
Secondary
Change From Baseline in Apolipoprotein A1
Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline apolipoprotein A1 as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Apolipoprotein A1 | Week 12 (n=140, 138, 137, 144) | -1.6 mg/dL | Standard Error 1.57 |
| Alogliptin 25 mg | Change From Baseline in Apolipoprotein A1 | Week 26 (n=149, 139, 146, 146) | -4.5 mg/dL | Standard Error 1.59 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 12 (n=140, 138, 137, 144) | 2.3 mg/dL | Standard Error 1.58 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 26 (n=149, 139, 146, 146) | 1.2 mg/dL | Standard Error 1.64 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 12 (n=140, 138, 137, 144) | 1.0 mg/dL | Standard Error 1.59 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 26 (n=149, 139, 146, 146) | 0.8 mg/dL | Standard Error 1.6 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 26 (n=149, 139, 146, 146) | 1.6 mg/dL | Standard Error 1.6 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A1 | Week 12 (n=140, 138, 137, 144) | 1.7 mg/dL | Standard Error 1.55 |
Secondary
Change From Baseline in Apolipoprotein A2
Change from Baseline in apolipoprotein A2 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein A2 as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Apolipoprotein A2 | Week 12 (n=140, 138, 137, 144) | -0.1 mg/dL | Standard Error 0.41 |
| Alogliptin 25 mg | Change From Baseline in Apolipoprotein A2 | Week 26 (n=149, 139, 146, 146) | -0.3 mg/dL | Standard Error 0.41 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 12 (n=140, 138, 137, 144) | 3.4 mg/dL | Standard Error 0.41 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 26 (n=149, 139, 146, 146) | 2.9 mg/dL | Standard Error 0.43 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 12 (n=140, 138, 137, 144) | 2.8 mg/dL | Standard Error 0.41 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 26 (n=149, 139, 146, 146) | 2.5 mg/dL | Standard Error 0.42 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 26 (n=149, 139, 146, 146) | 2.6 mg/dL | Standard Error 0.42 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein A2 | Week 12 (n=140, 138, 137, 144) | 3.2 mg/dL | Standard Error 0.4 |
Secondary
Change From Baseline in Apolipoprotein B
Change from Baseline in apolipoprotein B was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein B as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Apolipoprotein B | Week 12 (n=140, 138, 137, 143) | -4.0 mg/dL | Standard Error 1.76 |
| Alogliptin 25 mg | Change From Baseline in Apolipoprotein B | Week 26 (n=149, 139, 146, 146) | -2.5 mg/dL | Standard Error 1.84 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 26 (n=149, 139, 146, 146) | -3.7 mg/dL | Standard Error 1.91 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 12 (n=140, 138, 137, 143) | -5.0 mg/dL | Standard Error 1.78 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 12 (n=140, 138, 137, 143) | -9.8 mg/dL | Standard Error 1.78 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 26 (n=149, 139, 146, 146) | -7.9 mg/dL | Standard Error 1.86 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 12 (n=140, 138, 137, 143) | -5.9 mg/dL | Standard Error 1.74 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein B | Week 26 (n=149, 139, 146, 146) | -6.4 mg/dL | Standard Error 1.86 |
Secondary
Change From Baseline in Apolipoprotein C-III
Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein C-III as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Apolipoprotein C-III | Week 26 (n=149, 139, 147, 146) | -0.4 mg/dL | Standard Error 0.28 |
| Alogliptin 25 mg | Change From Baseline in Apolipoprotein C-III | Week 12 (n=140, 138, 138, 144) | -0.5 mg/dL | Standard Error 0.3 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 26 (n=149, 139, 147, 146) | -0.2 mg/dL | Standard Error 0.29 |
| Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 12 (n=140, 138, 138, 144) | -0.3 mg/dL | Standard Error 0.3 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 12 (n=140, 138, 138, 144) | -0.8 mg/dL | Standard Error 0.3 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 26 (n=149, 139, 147, 146) | -0.3 mg/dL | Standard Error 0.28 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 26 (n=149, 139, 147, 146) | -0.4 mg/dL | Standard Error 0.28 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Apolipoprotein C-III | Week 12 (n=140, 138, 138, 144) | -0.3 mg/dL | Standard Error 0.3 |
Secondary
Change From Baseline in Body Weight
Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline weight as a covariate.
Time frame: Baseline and Weeks 8, 12, 20 and 26.
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 | Change From Baseline in Body Weight | Week 20 (n=159, 147, 155, 154) | -0.47 kg | Standard Error 0.265 |
| Alogliptin 25 mg | Change From Baseline in Body Weight | Week 8 (n=155, 146, 152, 151) | -0.34 kg | Standard Error 0.184 |
| Alogliptin 25 mg | Change From Baseline in Body Weight | Week 26 (n=159, 147, 155, 154) | -0.29 kg | Standard Error 0.291 |
| Alogliptin 25 mg | Change From Baseline in Body Weight | Week 12 (n=159, 147, 155, 154) | -0.78 kg | Standard Error 0.227 |
| Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 8 (n=155, 146, 152, 151) | 0.58 kg | Standard Error 0.189 |
| Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 26 (n=159, 147, 155, 154) | 2.19 kg | Standard Error 0.302 |
| Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 20 (n=159, 147, 155, 154) | 1.56 kg | Standard Error 0.275 |
| Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 12 (n=159, 147, 155, 154) | 0.96 kg | Standard Error 0.236 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 12 (n=159, 147, 155, 154) | 1.35 kg | Standard Error 0.23 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 8 (n=155, 146, 152, 151) | 0.82 kg | Standard Error 0.185 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 20 (n=159, 147, 155, 154) | 2.36 kg | Standard Error 0.268 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 26 (n=159, 147, 155, 154) | 3.14 kg | Standard Error 0.295 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 26 (n=159, 147, 155, 154) | 2.51 kg | Standard Error 0.296 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 8 (n=155, 146, 152, 151) | 0.70 kg | Standard Error 0.186 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 12 (n=159, 147, 155, 154) | 1.22 kg | Standard Error 0.23 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Body Weight | Week 20 (n=159, 147, 155, 154) | 1.86 kg | Standard Error 0.269 |
Secondary
Change From Baseline in Calculated Homeostatic Model Assessment 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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA IR as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 12 (n=139, 132, 137, 143) | -0.814 insulin resistance | Standard Error 0.5309 |
| Alogliptin 25 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 26 (n=145, 134, 144, 148) | -1.353 insulin resistance | Standard Error 0.3566 |
| Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 12 (n=139, 132, 137, 143) | -3.479 insulin resistance | Standard Error 0.5458 |
| Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 26 (n=145, 134, 144, 148) | -3.350 insulin resistance | Standard Error 0.3717 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 12 (n=139, 132, 137, 143) | -2.905 insulin resistance | Standard Error 0.5348 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 26 (n=145, 134, 144, 148) | -3.646 insulin resistance | Standard Error 0.3579 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 26 (n=145, 134, 144, 148) | -3.508 insulin resistance | Standard Error 0.3532 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance | Week 12 (n=139, 132, 137, 143) | -3.877 insulin resistance | Standard Error 0.5236 |
Secondary
Change From Baseline in C-peptide Levels
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline C-peptide as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in C-peptide Levels | Week 20 (n=158, 150, 154, 156) | -0.097 ng/mL | Standard Error 0.0783 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Levels | Week 4 (n=142, 141, 141, 146) | 0.057 ng/mL | Standard Error 0.074 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Levels | Week 8 (n=158, 150, 153, 156) | 0.034 ng/mL | Standard Error 0.0701 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Levels | Week 16 (n=158, 150, 154, 156) | 0.037 ng/mL | Standard Error 0.0801 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Levels | Week 12 (n=158, 150, 154, 156) | -0.040 ng/mL | Standard Error 0.0676 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Levels | Week 26 (n=158, 150, 154, 156) | -0.068 ng/mL | Standard Error 0.0752 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 12 (n=158, 150, 154, 156) | -0.612 ng/mL | Standard Error 0.0693 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 4 (n=142, 141, 141, 146) | -0.551 ng/mL | Standard Error 0.0741 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 26 (n=158, 150, 154, 156) | -0.577 ng/mL | Standard Error 0.0771 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 8 (n=158, 150, 153, 156) | -0.606 ng/mL | Standard Error 0.0718 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 16 (n=158, 150, 154, 156) | -0.604 ng/mL | Standard Error 0.0822 |
| Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 20 (n=158, 150, 154, 156) | -0.623 ng/mL | Standard Error 0.0803 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 26 (n=158, 150, 154, 156) | -0.541 ng/mL | Standard Error 0.076 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 12 (n=158, 150, 154, 156) | -0.534 ng/mL | Standard Error 0.0684 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 16 (n=158, 150, 154, 156) | -0.424 ng/mL | Standard Error 0.081 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 4 (n=142, 141, 141, 146) | -0.593 ng/mL | Standard Error 0.0741 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 20 (n=158, 150, 154, 156) | -0.556 ng/mL | Standard Error 0.0792 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 8 (n=158, 150, 153, 156) | -0.620 ng/mL | Standard Error 0.0711 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 16 (n=158, 150, 154, 156) | -0.353 ng/mL | Standard Error 0.0805 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 4 (n=142, 141, 141, 146) | -0.452 ng/mL | Standard Error 0.0729 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 12 (n=158, 150, 154, 156) | -0.536 ng/mL | Standard Error 0.068 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 8 (n=158, 150, 153, 156) | -0.547 ng/mL | Standard Error 0.0704 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 20 (n=158, 150, 154, 156) | -0.374 ng/mL | Standard Error 0.0787 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in C-peptide Levels | Week 26 (n=158, 150, 154, 156) | -0.444 ng/mL | Standard Error 0.0756 |
Secondary
Change From Baseline in Fasting Plasma Glucose Over Time
The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline plasma glucose as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=162, 157, 162, 162) | -29.5 mg/dL | Standard Error 3.01 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=162, 157, 162, 162) | -28.3 mg/dL | Standard Error 3.06 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=162, 157, 162, 161) | -26.7 mg/dL | Standard Error 2.72 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=161, 156, 162, 159) | -16.7 mg/dL | Standard Error 2.87 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=162, 157, 162, 162) | -25.8 mg/dL | Standard Error 3.26 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=148, 146, 152, 151) | -14.6 mg/dL | Standard Error 2.93 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=162, 157, 162, 162) | -26.9 mg/dL | Standard Error 3.11 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=162, 157, 162, 162) | -29.0 mg/dL | Standard Error 2.8 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=162, 157, 162, 162) | -37.3 mg/dL | Standard Error 3.31 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=161, 156, 162, 159) | -14.2 mg/dL | Standard Error 2.92 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=162, 157, 162, 162) | -42.4 mg/dL | Standard Error 3.05 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=162, 157, 162, 161) | -31.9 mg/dL | Standard Error 2.76 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=162, 157, 162, 162) | -38.0 mg/dL | Standard Error 2.84 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=162, 157, 162, 162) | -42.0 mg/dL | Standard Error 3.11 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=162, 157, 162, 162) | -40.6 mg/dL | Standard Error 3.16 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=148, 146, 152, 151) | -7.3 mg/dL | Standard Error 2.95 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=162, 157, 162, 161) | -41.4 mg/dL | Standard Error 2.72 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=162, 157, 162, 162) | -52.7 mg/dL | Standard Error 3.12 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=162, 157, 162, 162) | -51.9 mg/dL | Standard Error 3.01 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=162, 157, 162, 162) | -50.2 mg/dL | Standard Error 3.27 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=162, 157, 162, 162) | -54.0 mg/dL | Standard Error 3.07 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=162, 157, 162, 162) | -50.4 mg/dL | Standard Error 2.8 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=148, 146, 152, 151) | -26.6 mg/dL | Standard Error 2.9 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=161, 156, 162, 159) | -33.5 mg/dL | Standard Error 2.87 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=148, 146, 152, 151) | -23.3 mg/dL | Standard Error 2.91 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=162, 157, 162, 162) | -48.4 mg/dL | Standard Error 2.81 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=162, 157, 162, 162) | -49.3 mg/dL | Standard Error 3.01 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=162, 157, 162, 162) | -48.5 mg/dL | Standard Error 3.27 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=162, 157, 162, 161) | -39.7 mg/dL | Standard Error 2.73 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=161, 156, 162, 159) | -30.9 mg/dL | Standard Error 2.9 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=162, 157, 162, 162) | -46.6 mg/dL | Standard Error 3.12 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=162, 157, 162, 162) | -47.5 mg/dL | Standard Error 3.07 |
Comparison: Comparison of change from Baseline in fasting plasma glucose at Week 26 between Pioglitazone 30 mg and Alogliptin 12.5 mg + Pioglitazone 30 mg.p-value: 0.01795% CI: [-20.3, -2]ANCOVA
Comparison: Comparison of change from Baseline in fasting plasma glucose at Week 26 between Pioglitazone 30 mg and Alogliptin 25 mg + Pioglitazone 30 mg.p-value: 0.00695% CI: [-22, -3.8]ANCOVA
Comparison: Comparison of change from Baseline in fasting plasma glucose at Week 26 between Alogliptin 25 mg and Alogliptin 25 mg + Pioglitazone 30 mg.p-value: <0.00195% CI: [-33.5, -15.4]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 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline proinsulin as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Fasting Proinsulin | Week 16 (n=150, 143, 147, 155) | -3.4 pmol/L | Standard Error 1.88 |
| Alogliptin 25 mg | Change From Baseline in Fasting Proinsulin | Week 26 (n=150, 143, 147, 155) | -4.8 pmol/L | Standard Error 1.64 |
| Alogliptin 25 mg | Change From Baseline in Fasting Proinsulin | Week 12 (n=150, 143, 147, 155) | -5.9 pmol/L | Standard Error 1.48 |
| Alogliptin 25 mg | Change From Baseline in Fasting Proinsulin | Week 20 (n=150, 143, 147, 155) | -8.1 pmol/L | Standard Error 1.75 |
| Alogliptin 25 mg | Change From Baseline in Fasting Proinsulin | Week 8 (n=150, 143, 146, 155) | -3.7 pmol/L | Standard Error 1.57 |
| Alogliptin 25 mg | Change From Baseline in Fasting Proinsulin | Week 4 (n=136, 134, 135, 145) | -4.9 pmol/L | Standard Error 1.74 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 20 (n=150, 143, 147, 155) | -16.1 pmol/L | Standard Error 1.79 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 8 (n=150, 143, 146, 155) | -14.9 pmol/L | Standard Error 1.6 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 26 (n=150, 143, 147, 155) | -13.2 pmol/L | Standard Error 1.68 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 12 (n=150, 143, 147, 155) | -16.0 pmol/L | Standard Error 1.52 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 4 (n=136, 134, 135, 145) | -12.1 pmol/L | Standard Error 1.75 |
| Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 16 (n=150, 143, 147, 155) | -16.3 pmol/L | Standard Error 1.93 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 26 (n=150, 143, 147, 155) | -18.3 pmol/L | Standard Error 1.66 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 8 (n=150, 143, 146, 155) | -18.2 pmol/L | Standard Error 1.59 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 20 (n=150, 143, 147, 155) | -19.8 pmol/L | Standard Error 1.76 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 16 (n=150, 143, 147, 155) | -16.0 pmol/L | Standard Error 1.9 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 4 (n=136, 134, 135, 145) | -16.0 pmol/L | Standard Error 1.74 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 12 (n=150, 143, 147, 155) | -18.6 pmol/L | Standard Error 1.5 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 26 (n=150, 143, 147, 155) | -15.1 pmol/L | Standard Error 1.61 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 4 (n=136, 134, 135, 145) | -12.3 pmol/L | Standard Error 1.68 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 8 (n=150, 143, 146, 155) | -17.7 pmol/L | Standard Error 1.54 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 12 (n=150, 143, 147, 155) | -16.7 pmol/L | Standard Error 1.46 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 16 (n=150, 143, 147, 155) | -13.1 pmol/L | Standard Error 1.85 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Fasting Proinsulin | Week 20 (n=150, 143, 147, 155) | -15.5 pmol/L | Standard Error 1.72 |
Secondary
Change From Baseline in Free Fatty Acids
Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline free fatty acid as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Free Fatty Acids | Week 26 (n=154, 136, 147, 150) | -0.0429 mmol/L | Standard Error 0.01624 |
| Alogliptin 25 mg | Change From Baseline in Free Fatty Acids | Week 12 (n=148, 136, 140, 147) | -0.0404 mmol/L | Standard Error 0.01643 |
| Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 26 (n=154, 136, 147, 150) | -0.0680 mmol/L | Standard Error 0.01729 |
| Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 12 (n=148, 136, 140, 147) | -0.0990 mmol/L | Standard Error 0.01716 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 26 (n=154, 136, 147, 150) | -0.0881 mmol/L | Standard Error 0.01662 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 12 (n=148, 136, 140, 147) | -0.1061 mmol/L | Standard Error 0.0169 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 26 (n=154, 136, 147, 150) | -0.1013 mmol/L | Standard Error 0.01647 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Free Fatty Acids | Week 12 (n=148, 136, 140, 147) | -0.0805 mmol/L | Standard Error 0.0165 |
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) at 4 week intervals during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16 and 20.
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 | Change From Baseline in HbA1c Over Time | Week 16 (n=160, 153, 158, 158) | -1.01 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Alogliptin 25 mg | Change From Baseline in HbA1c Over Time | Week 4 (n=145, 146, 144, 150) | -0.55 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Alogliptin 25 mg | Change From Baseline in HbA1c Over Time | Week 20 (n=160, 153, 158, 158) | -1.00 percentage of glycosylated hemoglobin | Standard Error 0.077 |
| Alogliptin 25 mg | Change From Baseline in HbA1c Over Time | Week 8 (n=160, 153, 158, 158) | -0.84 percentage of glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 25 mg | Change From Baseline in HbA1c Over Time | Week 12 (n=160, 153, 158, 158) | -0.98 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 8 (n=160, 153, 158, 158) | -0.72 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 16 (n=160, 153, 158, 158) | -1.17 percentage of glycosylated hemoglobin | Standard Error 0.082 |
| Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 20 (n=160, 153, 158, 158) | -1.20 percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 4 (n=145, 146, 144, 150) | -0.30 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 12 (n=160, 153, 158, 158) | -1.04 percentage of glycosylated hemoglobin | Standard Error 0.071 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 8 (n=160, 153, 158, 158) | -1.19 percentage of glycosylated hemoglobin | Standard Error 0.059 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 12 (n=160, 153, 158, 158) | -1.57 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 4 (n=145, 146, 144, 150) | -0.62 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 16 (n=160, 153, 158, 158) | -1.67 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 20 (n=160, 153, 158, 158) | -1.72 percentage of glycosylated hemoglobin | Standard Error 0.078 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 20 (n=160, 153, 158, 158) | -1.54 percentage of glycosylated hemoglobin | Standard Error 0.078 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 4 (n=145, 146, 144, 150) | -0.51 percentage of glycosylated hemoglobin | Standard Error 0.043 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 16 (n=160, 153, 158, 158) | -1.43 percentage of glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 12 (n=160, 153, 158, 158) | -1.34 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in HbA1c Over Time | Week 8 (n=160, 153, 158, 158) | -1.03 percentage of glycosylated hemoglobin | Standard Error 0.059 |
Comparison: Comparison of change from Baseline at Week 20 between Pioglitazone 30 mg and Alogliptin 12.5 mg + Pioglitazone 30 mg.p-value: 0.00395% CI: [-0.55, -0.12]ANCOVA
Comparison: Comparison of change from Baseline at Week 20 between Pioglitazone 30 mg and Alogliptin 25 mg + Pioglitazone 30 mg.p-value: <0.00195% CI: [-0.74, -0.3]ANCOVA
Comparison: Comparison of change from Baseline at Week 20 between Alogliptin 25 mg and Alogliptin 25 mg + Pioglitazone 30 mg.p-value: <0.00195% CI: [-0.94, -0.51]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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL cholesterol as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=160, 151, 154, 158) | 0.5 mg/dL | Standard Error 0.56 |
| Alogliptin 25 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=160, 151, 155, 158) | 0.9 mg/dL | Standard Error 0.64 |
| Alogliptin 25 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=160, 151, 155, 158) | 0.8 mg/dL | Standard Error 0.64 |
| Alogliptin 25 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=160, 151, 155, 158) | 0.5 mg/dL | Standard Error 0.59 |
| Alogliptin 25 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=160, 151, 155, 158) | 0.9 mg/dL | Standard Error 0.57 |
| Alogliptin 25 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=146, 144, 142, 149) | -0.2 mg/dL | Standard Error 0.54 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=160, 151, 155, 158) | 6.0 mg/dL | Standard Error 0.66 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=160, 151, 155, 158) | 4.7 mg/dL | Standard Error 0.6 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=160, 151, 154, 158) | 4.7 mg/dL | Standard Error 0.58 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=160, 151, 155, 158) | 5.2 mg/dL | Standard Error 0.58 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=160, 151, 155, 158) | 5.7 mg/dL | Standard Error 0.66 |
| Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=146, 144, 142, 149) | 3.0 mg/dL | Standard Error 0.54 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=146, 144, 142, 149) | 3.8 mg/dL | Standard Error 0.55 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=160, 151, 155, 158) | 6.0 mg/dL | Standard Error 0.58 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=160, 151, 155, 158) | 5.6 mg/dL | Standard Error 0.6 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=160, 151, 154, 158) | 5.0 mg/dL | Standard Error 0.57 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=160, 151, 155, 158) | 6.4 mg/dL | Standard Error 0.65 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=160, 151, 155, 158) | 6.2 mg/dL | Standard Error 0.65 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 20 (n=160, 151, 155, 158) | 5.6 mg/dL | Standard Error 0.59 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 26 (n=160, 151, 155, 158) | 6.2 mg/dL | Standard Error 0.64 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 16 (n=160, 151, 155, 158) | 5.9 mg/dL | Standard Error 0.57 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 12 (n=160, 151, 155, 158) | 6.5 mg/dL | Standard Error 0.65 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 8 (n=160, 151, 154, 158) | 4.8 mg/dL | Standard Error 0.57 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-Density Lipoprotein Cholesterol | Week 4 (n=146, 144, 142, 149) | 3.0 mg/dL | Standard Error 0.54 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL particles as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | -0.26 µmol/L | Standard Error 0.313 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | -0.06 µmol/L | Standard Error 0.197 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | -0.26 µmol/L | Standard Error 0.311 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | 0.18 µmol/L | Standard Error 0.35 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | 0.50 µmol/L | Standard Error 0.412 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 0.81 µmol/L | Standard Error 0.359 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | 1.24 µmol/L | Standard Error 0.412 |
| Alogliptin 25 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 0.07 µmol/L | Standard Error 0.195 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | 0.95 µmol/L | Standard Error 0.329 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | -0.68 µmol/L | Standard Error 0.423 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 1.14 µmol/L | Standard Error 0.207 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 1.67 µmol/L | Standard Error 0.377 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | 0.72 µmol/L | Standard Error 0.319 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 0.99 µmol/L | Standard Error 0.2 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | 0.92 µmol/L | Standard Error 0.359 |
| Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | -0.28 µmol/L | Standard Error 0.433 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 1.24 µmol/L | Standard Error 0.201 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | 1.19 µmol/L | Standard Error 0.32 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | 0.11 µmol/L | Standard Error 0.359 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 1.01 µmol/L | Standard Error 0.367 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 0.98 µmol/L | Standard Error 0.2 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | 1.60 µmol/L | Standard Error 0.32 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | -2.65 µmol/L | Standard Error 0.423 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | -1.58 µmol/L | Standard Error 0.421 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 1.03 µmol/L | Standard Error 0.359 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | 0.54 µmol/L | Standard Error 0.348 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | -1.63 µmol/L | Standard Error 0.413 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 1.31 µmol/L | Standard Error 0.197 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | -2.42 µmol/L | Standard Error 0.41 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | 1.30 µmol/L | Standard Error 0.312 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | 1.61 µmol/L | Standard Error 0.308 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High Density Lipoprotein (HDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 1.31 µmol/L | Standard Error 0.193 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline hsCRP as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=147, 134, 138, 146) | -0.4497 mg/L | Standard Error 0.41497 |
| Alogliptin 25 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=153, 135, 144, 149) | -0.1851 mg/L | Standard Error 0.42623 |
| Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=153, 135, 144, 149) | -1.0391 mg/L | Standard Error 0.45388 |
| Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=147, 134, 138, 146) | -1.7446 mg/L | Standard Error 0.43493 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=147, 134, 138, 146) | -1.5346 mg/L | Standard Error 0.42831 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=153, 135, 144, 149) | -1.9763 mg/L | Standard Error 0.43925 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 12 (n=147, 134, 138, 146) | -2.2771 mg/L | Standard Error 0.41646 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in High-sensitivity C-Reactive Protein | Week 26 (n=153, 135, 144, 149) | -1.9796 mg/L | Standard Error 0.43182 |
Secondary
Change From Baseline in Homeostatic Model Assessment 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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA beta cell function as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 26 (n=145, 134, 144, 148) | 10.472 percentage beta cell function | Standard Error 8.5306 |
| Alogliptin 25 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 12 (n= 139, 132, 137, 143) | 15.133 percentage beta cell function | Standard Error 4.2787 |
| Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 26 (n=145, 134, 144, 148) | 17.500 percentage beta cell function | Standard Error 8.8718 |
| Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 12 (n= 139, 132, 137, 143) | 17.328 percentage beta cell function | Standard Error 4.3868 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 26 (n=145, 134, 144, 148) | 39.153 percentage beta cell function | Standard Error 8.5455 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 12 (n= 139, 132, 137, 143) | 30.266 percentage beta cell function | Standard Error 4.3006 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 12 (n= 139, 132, 137, 143) | 22.134 percentage beta cell function | Standard Error 4.2098 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Homeostatic Model Assessment Beta Cell Function | Week 26 (n=145, 134, 144, 148) | 24.887 percentage beta cell function | Standard Error 8.4285 |
Secondary
Change From Baseline in Insulin
The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline insulin as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Insulin | Week 26 (n=150, 142, 148, 155) | -0.47 μIU/mL | Standard Error 0.755 |
| Alogliptin 25 mg | Change From Baseline in Insulin | Week 20 (n=150, 142, 148, 155) | -1.02 μIU/mL | Standard Error 0.844 |
| Alogliptin 25 mg | Change From Baseline in Insulin | Week 16 (n=150, 142, 148, 155) | 0.26 μIU/mL | Standard Error 0.829 |
| Alogliptin 25 mg | Change From Baseline in Insulin | Week 8 (n=150, 142, 147, 155) | 0.93 μIU/mL | Standard Error 0.811 |
| Alogliptin 25 mg | Change From Baseline in Insulin | Week 12 (n=150, 142, 148, 155) | 0.29 μIU/mL | Standard Error 0.883 |
| Alogliptin 25 mg | Change From Baseline in Insulin | Week 4 (n=135, 133, 133, 145) | 0.43 μIU/mL | Standard Error 0.684 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 4 (n=135, 133, 133, 145) | -4.74 μIU/mL | Standard Error 0.689 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 26 (n=150, 142, 148, 155) | -4.06 μIU/mL | Standard Error 0.776 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 8 (n=150, 142, 147, 155) | -4.41 μIU/mL | Standard Error 0.834 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 12 (n=150, 142, 148, 155) | -4.08 μIU/mL | Standard Error 0.907 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 16 (n=150, 142, 148, 155) | -4.49 μIU/mL | Standard Error 0.852 |
| Pioglitazone 30 mg | Change From Baseline in Insulin | Week 20 (n=150, 142, 148, 155) | -4.56 μIU/mL | Standard Error 0.868 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 20 (n=150, 142, 148, 155) | -4.61 μIU/mL | Standard Error 0.848 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 16 (n=150, 142, 148, 155) | -3.65 μIU/mL | Standard Error 0.833 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 12 (n=150, 142, 148, 155) | -2.98 μIU/mL | Standard Error 0.887 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 8 (n=150, 142, 147, 155) | -4.75 μIU/mL | Standard Error 0.818 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 4 (n=135, 133, 133, 145) | -4.67 μIU/mL | Standard Error 0.687 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 26 (n=150, 142, 148, 155) | -3.86 μIU/mL | Standard Error 0.759 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 4 (n=135, 133, 133, 145) | -4.27 μIU/mL | Standard Error 0.659 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 8 (n=150, 142, 147, 155) | -4.86 μIU/mL | Standard Error 0.797 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 20 (n=150, 142, 148, 155) | -3.06 μIU/mL | Standard Error 0.829 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 16 (n=150, 142, 148, 155) | -2.73 μIU/mL | Standard Error 0.814 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 26 (n=150, 142, 148, 155) | -3.72 μIU/mL | Standard Error 0.742 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Insulin | Week 12 (n=150, 142, 148, 155) | -4.65 μIU/mL | Standard Error 0.867 |
Secondary
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles
The change from Baseline in levels of IDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline IDL particles as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=139, 132, 132, 141) | -2.9 nmol/L | Standard Error 3.63 |
| Alogliptin 25 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=147, 133, 141, 147) | 0.5 nmol/L | Standard Error 3.68 |
| Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=147, 133, 141, 147) | 2.1 nmol/L | Standard Error 3.86 |
| Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=139, 132, 132, 141) | -1.0 nmol/L | Standard Error 3.72 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=147, 133, 141, 147) | -1.0 nmol/L | Standard Error 3.75 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=139, 132, 132, 141) | -2.9 nmol/L | Standard Error 3.73 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 12 (n=139, 132, 132, 141) | -4.0 nmol/L | Standard Error 3.61 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles | Week 26 (n=147, 133, 141, 147) | -5.8 nmol/L | Standard Error 3.68 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL cholesterol as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=137, 130, 135, 142) | -3.5 mg/dL | Standard Error 1.88 |
| Alogliptin 25 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=152, 139, 147, 153) | -0.5 mg/dL | Standard Error 1.96 |
| Alogliptin 25 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=154, 140, 148, 154) | 2.0 mg/dL | Standard Error 2.22 |
| Alogliptin 25 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=154, 140, 148, 154) | 0.8 mg/dL | Standard Error 2.02 |
| Alogliptin 25 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=154, 140, 148, 154) | 0.9 mg/dL | Standard Error 2.27 |
| Alogliptin 25 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=154, 140, 148, 154) | 1.8 mg/dL | Standard Error 2.22 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=152, 139, 147, 153) | 7.6 mg/dL | Standard Error 2.05 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=137, 130, 135, 142) | 2.8 mg/dL | Standard Error 1.93 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=154, 140, 148, 154) | 7.4 mg/dL | Standard Error 2.38 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=154, 140, 148, 154) | 5.8 mg/dL | Standard Error 2.12 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=154, 140, 148, 154) | 6.6 mg/dL | Standard Error 2.33 |
| Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=154, 140, 148, 154) | 8.1 mg/dL | Standard Error 2.33 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=152, 139, 147, 153) | 2.6 mg/dL | Standard Error 1.99 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=154, 140, 148, 154) | 5.3 mg/dL | Standard Error 2.27 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=154, 140, 148, 154) | 4.6 mg/dL | Standard Error 2.27 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=137, 130, 135, 142) | 2.2 mg/dL | Standard Error 1.89 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=154, 140, 148, 154) | 1.4 mg/dL | Standard Error 2.06 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=154, 140, 148, 154) | 2.1 mg/dL | Standard Error 2.32 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 20 (n=154, 140, 148, 154) | 0.5 mg/dL | Standard Error 2.27 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 8 (n=152, 139, 147, 153) | 1.3 mg/dL | Standard Error 1.95 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 16 (n=154, 140, 148, 154) | 4.6 mg/dL | Standard Error 2.22 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 26 (n=154, 140, 148, 154) | 3.8 mg/dL | Standard Error 2.22 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 12 (n=154, 140, 148, 154) | 3.9 mg/dL | Standard Error 2.02 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low-Density Lipoprotein Cholesterol | Week 4 (n=137, 130, 135, 142) | -2.8 mg/dL | Standard Error 1.85 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL particles as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 26 (n=147, 133, 141, 147) | 9.9 nmol/L | Standard Error 6.42 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 12 (n=139, 132, 132, 141) | -6.2 nmol/L | Standard Error 6.25 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -11.9 nmol/L | Standard Error 28.57 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 26 (n=147, 133, 141, 147) | 45.1 nmol/L | Standard Error 27.44 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 2.6 nmol/L | Standard Error 15.32 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 15.3 nmol/L | Standard Error 15.16 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 26 (n=147, 133, 141, 147) | 54.5 nmol/L | Standard Error 33.34 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 12 (n=139, 132, 132, 141) | -27.8 nmol/L | Standard Error 31.91 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 12 (n=139, 132, 132, 141) | -20.9 nmol/L | Standard Error 26.22 |
| Alogliptin 25 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 60.9 nmol/L | Standard Error 30.67 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 26 (n=147, 133, 141, 147) | -156.0 nmol/L | Standard Error 28.83 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -75.6 nmol/L | Standard Error 32.29 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 12 (n=139, 132, 132, 141) | -200.3 nmol/L | Standard Error 32.71 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 26 (n=147, 133, 141, 147) | -195.8 nmol/L | Standard Error 35.04 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 12 (n=139, 132, 132, 141) | -159.2 nmol/L | Standard Error 26.88 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -104.1 nmol/L | Standard Error 29.34 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 98.8 nmol/L | Standard Error 15.52 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 120.4 nmol/L | Standard Error 16.1 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 12 (n=139, 132, 132, 141) | -41.4 nmol/L | Standard Error 6.41 |
| Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 26 (n=147, 133, 141, 147) | -40.1 nmol/L | Standard Error 6.75 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 12 (n=139, 132, 132, 141) | -265.7 nmol/L | Standard Error 26.9 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -207.0 nmol/L | Standard Error 29.33 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 146.6 nmol/L | Standard Error 15.63 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 12 (n=139, 132, 132, 141) | -65.8 nmol/L | Standard Error 6.41 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 26 (n=147, 133, 141, 147) | -250.9 nmol/L | Standard Error 27.98 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 26 (n=147, 133, 141, 147) | -63.0 nmol/L | Standard Error 6.55 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 12 (n=139, 132, 132, 141) | -331.2 nmol/L | Standard Error 32.73 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 26 (n=147, 133, 141, 147) | -313.8 nmol/L | Standard Error 34.01 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -169.9 nmol/L | Standard Error 31.31 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 129.4 nmol/L | Standard Error 15.54 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -177.1 nmol/L | Standard Error 30.68 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | 142.1 nmol/L | Standard Error 15.05 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 26 (n=147, 133, 141, 147) | -66.6 nmol/L | Standard Error 6.41 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 12 (n=139, 132, 132, 141) | -254.2 nmol/L | Standard Error 26.02 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 26 (n=147, 133, 141, 147) | -327.4 nmol/L | Standard Error 33.3 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | 155.5 nmol/L | Standard Error 15.33 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Very Small - Week 26 (n=147, 133, 141, 147) | -260.8 nmol/L | Standard Error 27.4 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Small - Week 12 (n=139, 132, 132, 141) | -320.0 nmol/L | Standard Error 31.66 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -181.8 nmol/L | Standard Error 28.4 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Low Density Lipoprotein (LDL) Particles | Medium-Small - Week 12 (n=139, 132, 132, 141) | -65.8 nmol/L | Standard Error 6.2 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean HDL particle size as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Mean HDL Particle Size | Week 12 (n=139, 132, 132, 141) | -0.02 nm | Standard Error 0.024 |
| Alogliptin 25 mg | Change From Baseline in Mean HDL Particle Size | Week 26 (n=147, 133, 141, 147) | -0.03 nm | Standard Error 0.024 |
| Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.09 nm | Standard Error 0.025 |
| Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.08 nm | Standard Error 0.025 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.15 nm | Standard Error 0.024 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.17 nm | Standard Error 0.025 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.15 nm | Standard Error 0.024 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean HDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.14 nm | Standard Error 0.024 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean LDL particle size as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Mean LDL Particle Size | Week 26 (n=147, 133, 141, 147) | -0.02 nm | Standard Error 0.052 |
| Alogliptin 25 mg | Change From Baseline in Mean LDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.09 nm | Standard Error 0.051 |
| Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.44 nm | Standard Error 0.054 |
| Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.44 nm | Standard Error 0.053 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.65 nm | Standard Error 0.053 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.63 nm | Standard Error 0.053 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.61 nm | Standard Error 0.052 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean LDL Particle Size | Week 12 (n=139, 132, 132, 141) | 0.58 nm | Standard Error 0.051 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean VLDL particle size as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=139, 132, 132, 141) | -0.97 nm | Standard Error 0.668 |
| Alogliptin 25 mg | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=147, 133, 141, 147) | 0.30 nm | Standard Error 0.607 |
| Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=147, 133, 141, 147) | -3.71 nm | Standard Error 0.64 |
| Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=139, 132, 132, 141) | -3.97 nm | Standard Error 0.688 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=139, 132, 132, 141) | -2.92 nm | Standard Error 0.687 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=147, 133, 141, 147) | -4.21 nm | Standard Error 0.62 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 12 (n=139, 132, 132, 141) | -2.85 nm | Standard Error 0.665 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Mean VLDL Particle Size | Week 26 (n=147, 133, 141, 147) | -2.80 nm | Standard Error 0.607 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline NMR total triglycerides as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=139, 132, 132, 141) | -14.9 mg/dL | Standard Error 6.36 |
| Alogliptin 25 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=147, 133, 141, 147) | -7.6 mg/dL | Standard Error 5.82 |
| Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=147, 133, 141, 147) | -20.2 mg/dL | Standard Error 6.11 |
| Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=139, 132, 132, 141) | -25.0 mg/dL | Standard Error 6.52 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=139, 132, 132, 141) | -39.7 mg/dL | Standard Error 6.52 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=147, 133, 141, 147) | -28.8 mg/dL | Standard Error 5.94 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 12 (n=139, 132, 132, 141) | -23.7 mg/dL | Standard Error 6.32 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides | Week 26 (n=147, 133, 141, 147) | -22.6 mg/dL | Standard Error 5.82 |
Secondary
Change From Baseline in Plasminogen Activator Inhibitor-1
Change from Baseline in plasminogen activator inhibitor-1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline plasminogen activator inhibitor-1 as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=136, 127, 131, 133) | -1.58 ng/mL | Standard Error 2.815 |
| Alogliptin 25 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=145, 129, 142, 137) | 1.71 ng/mL | Standard Error 3.151 |
| Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=145, 129, 142, 137) | -5.45 ng/mL | Standard Error 3.341 |
| Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=136, 127, 131, 133) | -4.23 ng/mL | Standard Error 2.909 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=136, 127, 131, 133) | -9.63 ng/mL | Standard Error 2.87 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=145, 129, 142, 137) | -7.14 ng/mL | Standard Error 3.189 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 12 (n=136, 127, 131, 133) | -11.87 ng/mL | Standard Error 2.849 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Plasminogen Activator Inhibitor-1 | Week 26 (n=145, 129, 142, 137) | -8.38 ng/mL | Standard Error 3.246 |
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 and 26 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment and geographic region as class variables and Baseline proinsulin/insulin ratio as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=135, 133, 133, 145) | -0.073 ratio | Standard Error 0.015 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=149, 142, 146, 155) | -0.041 ratio | Standard Error 0.014 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=149, 142, 147, 155) | -0.051 ratio | Standard Error 0.0145 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=149, 142, 147, 155) | -0.062 ratio | Standard Error 0.0122 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=149, 142, 147, 155) | -0.049 ratio | Standard Error 0.0173 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=149, 142, 147, 155) | -0.057 ratio | Standard Error 0.0173 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=149, 142, 147, 155) | -0.098 ratio | Standard Error 0.0125 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=149, 142, 147, 155) | -0.081 ratio | Standard Error 0.0177 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=135, 133, 133, 145) | -0.047 ratio | Standard Error 0.0151 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=149, 142, 146, 155) | -0.085 ratio | Standard Error 0.0144 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=149, 142, 147, 155) | -0.076 ratio | Standard Error 0.0177 |
| Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=149, 142, 147, 155) | -0.076 ratio | Standard Error 0.0148 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=149, 142, 146, 155) | -0.094 ratio | Standard Error 0.0142 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=149, 142, 147, 155) | -0.123 ratio | Standard Error 0.0123 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=149, 142, 147, 155) | -0.115 ratio | Standard Error 0.0174 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=135, 133, 133, 145) | -0.080 ratio | Standard Error 0.0151 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=149, 142, 147, 155) | -0.107 ratio | Standard Error 0.0146 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=149, 142, 147, 155) | -0.124 ratio | Standard Error 0.0174 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 8 (n=149, 142, 146, 155) | -0.102 ratio | Standard Error 0.0138 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 4 (n=135, 133, 133, 145) | -0.056 ratio | Standard Error 0.0144 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=149, 142, 147, 155) | -0.095 ratio | Standard Error 0.012 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 20 (n=149, 142, 147, 155) | -0.119 ratio | Standard Error 0.0169 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 16 (n=149, 142, 147, 155) | -0.090 ratio | Standard Error 0.017 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=149, 142, 147, 155) | -0.102 ratio | Standard Error 0.0142 |
Secondary
Change From Baseline in Total Cholesterol Level
Change from Baseline in total cholesterol level was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline total cholesterol as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Total Cholesterol Level | Week 12 (n=160, 151, 155, 158) | -4.0 mg/dL | Standard Error 2.43 |
| Alogliptin 25 mg | Change From Baseline in Total Cholesterol Level | Week 8 (n=160, 151, 154, 158) | -5.4 mg/dL | Standard Error 2.3 |
| Alogliptin 25 mg | Change From Baseline in Total Cholesterol Level | Week 16 (n=160, 151, 155, 158) | -4.3 mg/dL | Standard Error 2.42 |
| Alogliptin 25 mg | Change From Baseline in Total Cholesterol Level | Week 26 (n=160, 151, 155, 158) | -0.5 mg/dL | Standard Error 2.61 |
| Alogliptin 25 mg | Change From Baseline in Total Cholesterol Level | Week 20 (n=160, 151, 155, 158) | -2.9 mg/dL | Standard Error 2.67 |
| Alogliptin 25 mg | Change From Baseline in Total Cholesterol Level | Week 4 (n=146, 144, 142, 149) | -8.5 mg/dL | Standard Error 2.22 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 12 (n=160, 151, 155, 158) | 4.9 mg/dL | Standard Error 2.51 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 4 (n=146, 144, 142, 149) | 0.9 mg/dL | Standard Error 2.23 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 8 (n=160, 151, 154, 158) | 7.2 mg/dL | Standard Error 2.37 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 26 (n=160, 151, 155, 158) | 6.5 mg/dL | Standard Error 2.68 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 16 (n=160, 151, 155, 158) | 4.6 mg/dL | Standard Error 2.49 |
| Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 20 (n=160, 151, 155, 158) | 4.5 mg/dL | Standard Error 2.75 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 4 (n=146, 144, 142, 149) | -0.4 mg/dL | Standard Error 2.25 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 8 (n=160, 151, 154, 158) | -0.3 mg/dL | Standard Error 2.34 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 12 (n=160, 151, 155, 158) | -0.6 mg/dL | Standard Error 2.47 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 16 (n=160, 151, 155, 158) | 3.8 mg/dL | Standard Error 2.46 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 20 (n=160, 151, 155, 158) | -0.3 mg/dL | Standard Error 2.71 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 26 (n=160, 151, 155, 158) | 3.7 mg/dL | Standard Error 2.65 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 26 (n=160, 151, 155, 158) | 4.0 mg/dL | Standard Error 2.62 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 20 (n=160, 151, 155, 158) | -0.6 mg/dL | Standard Error 2.69 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 16 (n=160, 151, 155, 158) | 4.7 mg/dL | Standard Error 2.44 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 12 (n=160, 151, 155, 158) | 4.4 mg/dL | Standard Error 2.45 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 8 (n=160, 151, 154, 158) | -1.2 mg/dL | Standard Error 2.31 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Total Cholesterol Level | Week 4 (n=146, 144, 142, 149) | -5.3 mg/dL | Standard Error 2.2 |
Secondary
Change From Baseline in Triglyceride Levels
Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline triglycerides as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 26.
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 | Change From Baseline in Triglyceride Levels | Week 16 (n=160, 151, 155, 158) | -44.5 mg/dL | Standard Error 5.74 |
| Alogliptin 25 mg | Change From Baseline in Triglyceride Levels | Week 4 (n=146, 144, 142, 149) | -28.2 mg/dL | Standard Error 8.6 |
| Alogliptin 25 mg | Change From Baseline in Triglyceride Levels | Week 26 (n=160, 151, 155, 158) | -24.7 mg/dL | Standard Error 6.83 |
| Alogliptin 25 mg | Change From Baseline in Triglyceride Levels | Week 12 (n=160, 151, 155, 158) | -36.4 mg/dL | Standard Error 6.9 |
| Alogliptin 25 mg | Change From Baseline in Triglyceride Levels | Week 8 (n=160, 151, 154, 158) | -34.8 mg/dL | Standard Error 6.51 |
| Alogliptin 25 mg | Change From Baseline in Triglyceride Levels | Week 20 (n=160, 151, 155, 158) | -29.9 mg/dL | Standard Error 7.35 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 4 (n=146, 144, 142, 149) | -43.2 mg/dL | Standard Error 8.63 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 16 (n=160, 151, 155, 158) | -48.3 mg/dL | Standard Error 5.9 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 20 (n=160, 151, 155, 158) | -46.6 mg/dL | Standard Error 7.56 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 8 (n=160, 151, 154, 158) | -38.2 mg/dL | Standard Error 6.69 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 12 (n=160, 151, 155, 158) | -47.9 mg/dL | Standard Error 7.09 |
| Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 26 (n=160, 151, 155, 158) | -46.6 mg/dL | Standard Error 7.02 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 8 (n=160, 151, 154, 158) | -61.6 mg/dL | Standard Error 6.63 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 4 (n=146, 144, 142, 149) | -51.7 mg/dL | Standard Error 8.7 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 20 (n=160, 151, 155, 158) | -59.3 mg/dL | Standard Error 7.46 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 16 (n=160, 151, 155, 158) | -54.6 mg/dL | Standard Error 5.82 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 26 (n=160, 151, 155, 158) | -56.2 mg/dL | Standard Error 6.92 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 12 (n=160, 151, 155, 158) | -64.3 mg/dL | Standard Error 7 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 16 (n=160, 151, 155, 158) | -43.9 mg/dL | Standard Error 5.78 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 8 (n=160, 151, 154, 158) | -51.9 mg/dL | Standard Error 6.56 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 12 (n=160, 151, 155, 158) | -45.4 mg/dL | Standard Error 6.95 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 20 (n=160, 151, 155, 158) | -46.5 mg/dL | Standard Error 7.41 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 4 (n=146, 144, 142, 149) | -32.1 mg/dL | Standard Error 8.51 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Triglyceride Levels | Week 26 (n=160, 151, 155, 158) | -43.1 mg/dL | Standard Error 6.88 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron particles as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -4.97 nmol/L | Standard Error 2.831 |
| Alogliptin 25 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | -0.94 nmol/L | Standard Error 0.511 |
| Alogliptin 25 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -6.59 nmol/L | Standard Error 2.6 |
| Alogliptin 25 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | -0.18 nmol/L | Standard Error 0.48 |
| Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | -1.96 nmol/L | Standard Error 0.505 |
| Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | 0.70 nmol/L | Standard Error 2.663 |
| Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | -1.83 nmol/L | Standard Error 0.525 |
| Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | 4.94 nmol/L | Standard Error 2.976 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | -2.63 nmol/L | Standard Error 0.525 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | -2.37 nmol/L | Standard Error 0.49 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -0.73 nmol/L | Standard Error 2.888 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -9.63 nmol/L | Standard Error 2.664 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 26 (n=147, 133, 141, 147) | -1.17 nmol/L | Standard Error 2.828 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 12 (n=139, 132, 132, 141) | -2.06 nmol/L | Standard Error 0.508 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Total Particles - Week 12 (n=139, 132, 132, 141) | -2.67 nmol/L | Standard Error 2.578 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles | Large Particles - Week 26 (n=147, 133, 141, 147) | -2.11 nmol/L | Standard Error 0.48 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron triglycerides as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=147, 133, 141, 147) | -8.2 mg/dL | Standard Error 5.79 |
| Alogliptin 25 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=139, 132, 132, 141) | -14.4 mg/dL | Standard Error 6.34 |
| Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=139, 132, 132, 141) | -25.6 mg/dL | Standard Error 6.5 |
| Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=147, 133, 141, 147) | -22.0 mg/dL | Standard Error 6.08 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=139, 132, 132, 141) | -39.5 mg/dL | Standard Error 6.5 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=147, 133, 141, 147) | -29.7 mg/dL | Standard Error 5.9 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 26 (n=147, 133, 141, 147) | -23.3 mg/dL | Standard Error 5.79 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL / Chylomicron Triglycerides | Week 12 (n=139, 132, 132, 141) | -24.2 mg/dL | Standard Error 6.3 |
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 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL particles as a covariate.
Time frame: Baseline and Weeks 12 and 26.
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 | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | -4.11 nmol/L | Standard Error 1.71 |
| Alogliptin 25 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | -3.20 nmol/L | Standard Error 1.639 |
| Alogliptin 25 mg | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | -1.74 nmol/L | Standard Error 1.617 |
| Alogliptin 25 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | -0.23 nmol/L | Standard Error 1.784 |
| Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | 4.77 nmol/L | Standard Error 1.662 |
| Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | 7.16 nmol/L | Standard Error 1.802 |
| Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | -0.39 nmol/L | Standard Error 1.874 |
| Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | -2.30 nmol/L | Standard Error 1.678 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | -8.52 nmol/L | Standard Error 1.679 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | -3.76 nmol/L | Standard Error 1.819 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | 1.18 nmol/L | Standard Error 1.66 |
| Alogliptin 25 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | 5.22 nmol/L | Standard Error 1.746 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 26 (n=147, 133, 141, 147) | 4.36 nmol/L | Standard Error 1.711 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 12 (n=139, 132, 132, 141) | -4.69 nmol/L | Standard Error 1.625 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Medium Particles - Week 26 (n=147, 133, 141, 147) | -3.58 nmol/L | Standard Error 1.782 |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Change From Baseline in VLDL Particles | Small Particles - Week 12 (n=139, 132, 132, 141) | 3.71 nmol/L | Standard Error 1.607 |
Secondary
Percentage of Participants Meeting Rescue Criteria
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days after the first sample and analyzed by the central laboratory: 1. After more than 4 weeks of treatment but prior to the Week 8 Visit: a single fasting plasma glucose ≥310 mg/dL (≥17.5 mmol/L); 2. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥275 mg/dL (≥15.27 mmol/L); 3. 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: Weeks 4, 8, 12, 16, 20 and 26.
Population: Full analysis set including patients with visits during or after the specified interval in each treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Overall (n=160, 156, 161, 160) | 11.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Week 12 to < Week 16 (n=156, 145, 153, 144) | 2.6 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Week 16 to < Week 20 (n=150, 138, 149, 134) | 7.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Week 20 to Week 26 (n=132, 133, 146, 130) | 0.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Week 8 to < Week 12 (n=158, 151, 157, 153) | 1.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants Meeting Rescue Criteria | Week 4 to < Week 8 (n=160, 156, 161, 160) | 0 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Overall (n=160, 156, 161, 160) | 6.4 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 8 to < Week 12 (n=158, 151, 157, 153) | 0 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 12 to < Week 16 (n=156, 145, 153, 144) | 3.4 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 4 to < Week 8 (n=160, 156, 161, 160) | 0 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 20 to Week 26 (n=132, 133, 146, 130) | 1.5 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 16 to < Week 20 (n=150, 138, 149, 134) | 2.2 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Overall (n=160, 156, 161, 160) | 2.5 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 8 to < Week 12 (n=158, 151, 157, 153) | 0 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 12 to < Week 16 (n=156, 145, 153, 144) | 1.3 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 16 to < Week 20 (n=150, 138, 149, 134) | 0 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 20 to Week 26 (n=132, 133, 146, 130) | 1.4 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 4 to < Week 8 (n=160, 156, 161, 160) | 0 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 12 to < Week 16 (n=156, 145, 153, 144) | 2.1 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 4 to < Week 8 (n=160, 156, 161, 160) | 0.6 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 20 to Week 26 (n=132, 133, 146, 130) | 0 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Overall (n=160, 156, 161, 160) | 3.8 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 8 to < Week 12 (n=158, 151, 157, 153) | 0 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants Meeting Rescue Criteria | Week 16 to < Week 20 (n=150, 138, 149, 134) | 1.5 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 0.5%.
Time frame: Baseline and Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% | 66.5 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% | 70.6 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% | 89.6 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% | 85.3 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1%.
Time frame: Baseline and Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% | 43.3 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% | 54.6 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% | 75.6 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% | 68.1 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%.
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1.5%.
Time frame: Baseline and Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. | 29.3 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. | 33.1 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. | 57.3 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. | 50.9 percentage of participants |
Secondary
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0%
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 2.0%.
Time frame: Baseline and Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% | 17.7 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% | 19.6 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% | 34.1 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% | 33.1 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤6.5%.
Time frame: Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% | 11.6 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% | 16.6 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% | 27.4 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% | 26.4 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7%.
Time frame: Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% | 24.4 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% | 33.7 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% | 62.8 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% | 53.4 percentage of participants |
Secondary
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5%
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7.5%.
Time frame: Week 26
Population: Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% | 44.5 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% | 55.8 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% | 72.0 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% | 72.4 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. Study week windows are defined to place hyperglycemia into visit categories.
Time frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Population: Full analysis set including patients with at least one non-missing fasting plasma glucose result in the specified interval in each treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 1 to < Week 4 (n=162, 157, 162, 161) | 31.5 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 16 to < Week 20 (n=142, 135, 144, 131) | 16.2 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to < Week 16 (n=153, 141, 148, 139) | 16.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n=162, 157, 162, 162) | 44.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 20 to Week 26 (n=130, 132, 143, 128) | 17.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to < Week 8 (n=153, 147, 148, 147) | 19.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to < Week 12 (n=151, 146, 152, 146) | 15.2 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 16 to < Week 20 (n=142, 135, 144, 131) | 14.8 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to < Week 12 (n=151, 146, 152, 146) | 11.6 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to < Week 8 (n=153, 147, 148, 147) | 15.0 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to < Week 16 (n=153, 141, 148, 139) | 9.2 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 1 to < Week 4 (n=162, 157, 162, 161) | 31.8 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 20 to Week 26 (n=130, 132, 143, 128) | 11.4 percentage of participants |
| Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n=162, 157, 162, 162) | 38.2 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to < Week 12 (n=151, 146, 152, 146) | 7.2 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n=162, 157, 162, 162) | 25.3 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 1 to < Week 4 (n=162, 157, 162, 161) | 18.5 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to < Week 8 (n=153, 147, 148, 147) | 10.8 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to < Week 16 (n=153, 141, 148, 139) | 8.1 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 16 to < Week 20 (n=142, 135, 144, 131) | 2.8 percentage of participants |
| Alogliptin 25 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 20 to Week 26 (n=130, 132, 143, 128) | 10.5 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to < Week 8 (n=153, 147, 148, 147) | 14.3 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 20 to Week 26 (n=130, 132, 143, 128) | 6.3 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 16 to < Week 20 (n=142, 135, 144, 131) | 6.9 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 1 to < Week 4 (n=162, 157, 162, 161) | 28.6 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n=162, 157, 162, 162) | 30.9 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to < Week 16 (n=153, 141, 148, 139) | 7.9 percentage of participants |
| Alogliptin 12.5 mg + Pioglitazone 30 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to < Week 12 (n=151, 146, 152, 146) | 8.2 percentage of participants |