Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00328627

Collaborator

(none)

1,554

Enrollment

Locations

Arms

Duration (Months)

17.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Alogliptin Drug: Alogliptin placebo Drug: Pioglitazone Drug: Pioglitazone placebo	Phase 3

Detailed Description

Over the past 30 years, the prevalence of diabetes has increased dramatically throughout the world due to population growth, aging, urbanization, increasing obesity, and physical inactivity. The total number of people with type 2 diabetes mellitus is projected to rise from 171 million in 2000 to 366 million in 2030. The incidence of type 2 diabetes mellitus in the United States alone is expected to increase from approximately 17 to 30.3 million by the year 2030. Type 2 diabetes mellitus is associated with a number of long-term microvascular and macrovascular complications associated with a reduced quality of life and increased morbidity and mortality. It is anticipated that the increasing incidence of type 2 diabetes mellitus will place an ever-increasing burden on families, increase national expenditures for health care services, and decrease worker productivity.

Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha-glucosidase, analogs of glucagon-like peptide-1 and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have achieving the target glycosylated hemoglobin level less than 7%.

SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus.

Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.

Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion) and pioglitazone (enhancement of insulin sensitivity), the goal of this study is to evaluate the efficacy of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on metformin. Study participation is anticipated to be approximately 7 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

1554 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of the Combination of SYR-322 (SYR110322) and Pioglitazone HCl (ACTOS®), in Subjects With Type 2 Diabetes

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin placebo Alogliptin placebo-matching tablets. Drug: Pioglitazone placebo Pioglitazone placebo-matching tablets.
Experimental: Alogliptin 12.5 + Placebo Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone placebo Pioglitazone placebo-matching tablets.
Experimental: Alogliptin 25 + Placebo Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone placebo Pioglitazone placebo-matching tablets.
Active Comparator: Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Active Comparator: Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin placebo Alogliptin placebo-matching tablets. Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Active Comparator: Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin placebo Alogliptin placebo-matching tablets. Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®
Experimental: Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322 Drug: Pioglitazone Pioglitazone tablets. Other Names: ACTOS®

Outcome Measures

Primary Outcome Measures

Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis) [Baseline and Week 26]
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).
Change From Baseline to Week 26 in HbA1c [Baseline and Week 26]
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

Secondary Outcome Measures

Change From Baseline in HbA1c Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16 and 20.]
The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.
Change From Baseline to Week 4 in HbA1c [Baseline and Week 4]
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Change From Baseline to Week 8 in HbA1c [Baseline and Week 8]
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Change From Baseline to Week 12 in HbA1c [Baseline and Week 12]
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Change From Baseline to Week 16 in HbA1c [Baseline and Week 16]
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Change From Baseline to Week 20 in HbA1c [Baseline and Week 20]
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) [Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.]
The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 1 in Fasting Plasma Glucose [Baseline and Week 1]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 2 in Fasting Plasma Glucose [Baseline and Week 2]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 4 in Fasting Plasma Glucose [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 8 in Fasting Plasma Glucose [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 12 in Fasting Plasma Glucose [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 16 in Fasting Plasma Glucose [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 20 in Fasting Plasma Glucose [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Change From Baseline to Week 26 in Fasting Plasma Glucose [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Percentage of Participants With Marked Hyperglycemia (Grouped Analysis) [From Week 1 to Week 26]
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With Marked Hyperglycemia [From Week 1 to Week 26]
Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
Percentage of Participants Meeting Rescue Criteria (Grouped Analysis) [From Week 1 to Week 26.]
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Percentage of Participants Meeting Rescue Criteria [From Week 1 to Week 26]
Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis) [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis) [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7% [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis) [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% [Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis) [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis) [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis) [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis) [Baseline and Week 26.]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2% [Baseline and Week 26]
Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.
Change From Baseline to Week 4 in Fasting Proinsulin [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline to Week 8 in Fasting Proinsulin [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline to Week 12 in Fasting Proinsulin [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline to Week 16 in Fasting Proinsulin [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline to Week 20 in Fasting Proinsulin [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline to Week 26 in Fasting Proinsulin [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Change From Baseline in Insulin Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 4 in Insulin Levels [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 8 in Insulin Levels [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 12 in Insulin Levels [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 16 in Insulin Levels [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 20 in Insulin Levels [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline to Week 26 in Insulin Levels [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 4 in Proinsulin/Insulin Ratio [Baseline and Week 4]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 8 in Proinsulin/Insulin Ratio [Baseline and Week 8]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 12 in Proinsulin/Insulin Ratio [Baseline and Week 12]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 16 in Proinsulin/Insulin Ratio [Baseline and Week 16]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 20 in Proinsulin/Insulin Ratio [Baseline and Week 20]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline to Week 26 in Proinsulin/Insulin Ratio [Baseline and Week 26]
The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Change From Baseline in C-peptide Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 4 in C-peptide Levels [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 8 in C-peptide Levels [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 12 in C-peptide Levels [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 16 in C-peptide Levels [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 20 in C-peptide Levels [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline to Week 26 in C-peptide Levels [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 4 in Total Cholesterol Levels [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 8 in Total Cholesterol Levels [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 12 in Total Cholesterol Levels [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 16 in Total Cholesterol Levels [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 20 in Total Cholesterol Levels [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline to Week 26 in Total Cholesterol Levels [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Change From Baseline in Triglycerides Over Time (Grouped Analysis) [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]
Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 4 in Triglyceride Levels [Baseline and Week 4]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 8 in Triglyceride Levels [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 12 in Triglyceride Levels [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 16 in Triglyceride Levels [Baseline and Week 16]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 20 in Triglyceride Levels [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline to Week 26 in Triglyceride Levels [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Change From Baseline to Week 12 in Free Fatty Acids [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Change From Baseline to Week 26 in Free Fatty Acids [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1 [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1 [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Change From Baseline in Adiponectin Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Change From Baseline to Week 12 in Adiponectin [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Change From Baseline to Week 26 in Adiponectin [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Change From Baseline in Body Weight Over Time (Grouped Analysis) [Baseline and Weeks 8, 12, 20 and 26.]
Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Change From Baseline to Week 8 in Body Weight [Baseline and Week 8]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Change From Baseline to Week 12 in Body Weight [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Change From Baseline to Week 20 in Body Weight [Baseline and Week 20]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Change From Baseline to Week 26 in Body Weight [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) [Baseline and Weeks 12 and 26.]
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance [Baseline and Week 12]
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance [Baseline and Week 26]
The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) [Baseline and Weeks 12 and 26]
The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function [Baseline and Week 12]
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function [Baseline and Week 26]
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Change From Baseline to Week 12 in Apolipoprotein A1 [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Change From Baseline to Week 26 in Apolipoprotein A1 [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Change From Baseline to Week 12 in Apolipoprotein A2 [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Change From Baseline to Week 26 in Apolipoprotein A2 [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Change From Baseline to Week 12 in Apolipoprotein B [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Change From Baseline to Week 26 in Apolipoprotein B [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Change From Baseline to Week 12 in Apolipoprotein C-III [Baseline and Week 12]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Change From Baseline to Week 26 in Apolipoprotein C-III [Baseline and Week 26]
Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides [Baseline and Week 12]
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides [Baseline and Week 26]
NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Change From Baseline to Week 12 in VLDL / Chylomicron Particles [Baseline and Week 12]
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Change From Baseline to Week 26 in VLDL / Chylomicron Particles [Baseline and Week 26]
The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides [Baseline and Week 12]
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides [Baseline and Week 26]
The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Change From Baseline in VLDL Particles Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Change From Baseline to Week 12 in VLDL Particles [Baseline and Week 12]
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Change From Baseline to Week 26 in VLDL Particles [Baseline and Week 26]
The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates
Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Change From Baseline to Week 12 in Mean VLDL Particle Size [Baseline and Week 12]
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Change From Baseline to Week 26 in Mean VLDL Particle Size [Baseline and Week 26]
The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Change From Baseline to Week 12 in IDL Particles [Baseline and Week 12]
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Change From Baseline to Week 26 in IDL Particles [Baseline and Week 26]
The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Change From Baseline to Week 12 in LDL Particles [Baseline and Week 12]
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Change From Baseline to Week 26 in LDL Particles [Baseline and Week 26]
The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Change From Baseline to Week 12 in Mean LDL Particle Size [Baseline and Week 12]
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Change From Baseline to Week 26 in Mean LDL Particle Size [Baseline and Week 26]
The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26.]
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Change From Baseline to Week 12 in HDL Particles [Baseline and Week 12]
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Change From Baseline to Week 26 in HDL Particles [Baseline and Week 26]
The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) [Baseline and Weeks 12 and 26]
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Change From Baseline to Week 12 in Mean HDL Particle Size [Baseline and Week 12]
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Change From Baseline to Week 26 in Mean HDL Particle Size [Baseline and Week 26]
The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women with a historical diagnosis of type 2 diabetes mellitus who were treated with metformin greater than or equal to 1500 mg alone but were experiencing inadequate glycemic control.
A stable dose of metformin of greater than or equal to 1500 mg or maximum tolerated dose.
No treatment with antidiabetic agents other than metformin within the 2 months prior to Screening.
A body mass index greater than or equal to 23 kg/m^{2 and less than or equal to 45
kg/m}2.
Fasting C-peptide greater than or equal to 0.8 ng/mL.
Regular use of other, non-excluded medications was allowed if a stable dose had been established for at least 4 weeks prior to Screening.
Systolic blood pressure less than or equal to 160 mmHg and diastolic pressure less than or equal to 100 mmHg.
Hemoglobin greater than or equal to 12 g/dL for men and greater than or equal to 10 g/dL for women.
Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal.
Serum creatinine less than 1.5 mg/dL for men and less than 1.4 mg/dL for women.
Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject was clinically euthyroid.
Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
No major illness or debility that in the investigator's opinion prohibited the patient from completing the study.

Exclusion Criteria:

Urine albumin/creatinine ratio greater than 113 mg/mmol at Screening.
A history of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 5 years prior to Screening.
A history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
A history of treated diabetic gastroparesis.
New York Heart Association Class III or IV heart failure regardless of therapy.
History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.
History of any hemoglobinopathy.
History of infection with hepatitis B, hepatitis C or human immunodeficiency virus.
History of a psychiatric disorder that could have affected the patient's ability to participate in the study.
History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
A history of alcohol or substance abuse within 2 years prior to Screening.
Receipt of any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening.
Previous participation in an investigational study of alogliptin.
Hypersensitive to pioglitazone, alogliptin, or other excipients.

Contacts and Locations

Locations

	City	State	Country
1	Birmingham	Alabama	United States
2	Columbiana	Alabama	United States
3	Huntsville	Alabama	United States
4	Phoenix	Arizona	United States
5	Little Rock	Arkansas	United States
6	Searcy	Arkansas	United States
7	Sherwood	Arkansas	United States
8	Burbank	California	United States
9	Foothill Ranch	California	United States
10	Irvine	California	United States
11	Sacramento	California	United States
12	San Diego	California	United States
13	Temecula	California	United States
14	Tustin	California	United States
15	Colorado Springs	Colorado	United States
16	Washington	District of Columbia	United States
17	Hollywood	Florida	United States
18	Kissimmee	Florida	United States
19	Miami	Florida	United States
20	New Port Richey	Florida	United States
21	Pembroke Pines	Florida	United States
22	Pinellas Park	Florida	United States
23	Sarasota	Florida	United States
24	Vero Beach	Florida	United States
25	Atlanta	Georgia	United States
26	Roswell	Georgia	United States
27	Savannah	Georgia	United States
28	Warner Robins	Georgia	United States
29	Chicago	Illinois	United States
30	Peoria	Illinois	United States
31	Lafayette	Indiana	United States
32	South Bend	Indiana	United States
33	Waterloo	Iowa	United States
34	Munfordville	Kentucky	United States
35	Baton Rouge	Louisiana	United States
36	Marrero	Louisiana	United States
37	Elkridge	Maryland	United States
38	Prince Frederick	Maryland	United States
39	Towson	Maryland	United States
40	Marlborough	Massachusetts	United States
41	Ann Arbor	Michigan	United States
42	Cadillac	Michigan	United States
43	Detroit	Michigan	United States
44	Livonia	Michigan	United States
45	Kansas City	Missouri	United States
46	North Las Vegas	Nevada	United States
47	Blackwood	New Jersey	United States
48	Trenton	New Jersey	United States
49	New York	New York	United States
50	Charlotte	North Carolina	United States
51	Statesville	North Carolina	United States
52	Gallipolis	Ohio	United States
53	Marion	Ohio	United States
54	Clinton	Oklahoma	United States
55	Oklahoma City	Oklahoma	United States
56	Tulsa	Oklahoma	United States
57	Allentown	Pennsylvania	United States
58	Altoona	Pennsylvania	United States
59	Philadelphia	Pennsylvania	United States
60	Pittsburgh	Pennsylvania	United States
61	Alcoa	Tennessee	United States
62	Milan	Tennessee	United States
63	Morristown	Tennessee	United States
64	Arlington	Texas	United States
65	Carrollton	Texas	United States
66	Dallas	Texas	United States
67	Fort Worth	Texas	United States
68	Houston	Texas	United States
69	San Antonio	Texas	United States
70	Temple	Texas	United States
71	Salt Lake City	Utah	United States
72	Burlington	Vermont	United States
73	Multiple Cities		Australia
74	Multiple Cities		Brazil
75	Multiple Cities		Bulgaria
76	Multiple Cities		Chile
77	Multiple Cities		Croatia
78	Multiple Cities		Estonia
79	Multiple Cities		Guatemala
80	Multiple Cities		India
81	Multiple Cities		Israel
82	Multiple Cities		Latvia
83	Multiple Cities		Mexico
84	Multiple Cities		New Zealand
85	Multiple Cities		Peru
86	Multiple Cities		Romania
87	Multiple Cities		Russian Federation
88	Multiple Cities		Serbia
89	Multiple Cities		South Africa
90	Multiple Cities		Ukraine

Sponsors and Collaborators

Takeda

Investigators

Study Director: VP Biological Sciences, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

ACTOS® Package Insert

Publications

None provided.

Responsible Party:

Takeda

ClinicalTrials.gov Identifier:

NCT00328627

Other Study ID Numbers:

01-05-TL-322OPI-001
2006-000694-30
U1111-1113-8587

First Posted:

May 22, 2006

Last Update Posted:

Apr 4, 2013

Last Verified:

Feb 1, 2013

Keywords provided by Takeda

Diabetes Mellitus, Type 2

Drug Therapy

Diabetes Mellitus, Non Insulin Dependent

Glucose Intolerance

Hyperglycemia

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Pioglitazone

Alogliptin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 327 investigative sites in 20 countries from 31 May 2006 to 17 March 2008.
Pre-assignment Detail	Participants with a diagnosis of type 2 diabetes who were inadequately controlled on a regimen of metformin alone were equally randomized to 1 of 12 double-blind treatment groups.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Period Title: Overall Study
STARTED	129	128	129	130	130	130	129	130	130	129	130	130
Safety Set	129	128	129	129	130	130	129	130	130	129	130	130
COMPLETED	70	97	101	93	115	110	94	116	113	97	112	114
NOT COMPLETED	59	31	28	37	15	20	35	14	17	32	18	16

Baseline Characteristics

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45	Total
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Total of all reporting groups
Overall Participants	129	128	129	130	130	130	129	130	130	129	130	130	1554
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (9.89)	53.1 (9.59)	53.7 (9.31)	54.1 (9.54)	53.6 (9.91)	54.9 (9.18)	56.1 (9.43)	55.0 (9.07)	54.4 (9.69)	54.5 (9.70)	54.0 (9.82)	54.2 (8.86)	54.4 (9.50)
Age, Customized (participants) [Number]
<65 years	106 82.2%	116 90.6%	112 86.8%	113 86.9%	109 83.8%	112 86.2%	101 78.3%	111 85.4%	107 82.3%	112 86.8%	111 85.4%	112 86.2%	1322 85.1%
≥65 years	23 17.8%	12 9.4%	17 13.2%	17 13.1%	21 16.2%	18 13.8%	28 21.7%	19 14.6%	23 17.7%	17 13.2%	19 14.6%	18 13.8%	232 14.9%
Sex: Female, Male (Count of Participants)
Female	68 52.7%	61 47.7%	79 61.2%	69 53.1%	70 53.8%	69 53.1%	66 51.2%	76 58.5%	75 57.7%	76 58.9%	70 53.8%	78 60%	857 55.1%
Male	61 47.3%	67 52.3%	50 38.8%	61 46.9%	60 46.2%	61 46.9%	63 48.8%	54 41.5%	55 42.3%	53 41.1%	60 46.2%	52 40%	697 44.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	63 48.8%	60 46.9%	63 48.8%	63 48.5%	55 42.3%	57 43.8%	67 51.9%	66 50.8%	62 47.7%	61 47.3%	63 48.5%	65 50%	745 47.9%
Not Hispanic or Latino	66 51.2%	68 53.1%	66 51.2%	67 51.5%	75 57.7%	73 56.2%	62 48.1%	64 49.2%	68 52.3%	68 52.7%	67 51.5%	65 50%	809 52.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	2 1.5%	2 1.5%	0 0%	1 0.8%	0 0%	0 0%	0 0%	0 0%	5 0.3%
Asian	5 3.9%	14 10.9%	15 11.6%	11 8.5%	9 6.9%	7 5.4%	10 7.8%	5 3.8%	12 9.2%	12 9.3%	8 6.2%	12 9.2%	120 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	8 6.2%	6 4.7%	5 3.9%	8 6.2%	4 3.1%	3 2.3%	6 4.7%	2 1.5%	5 3.8%	9 7%	9 6.9%	3 2.3%	68 4.4%
White	93 72.1%	89 69.5%	80 62%	85 65.4%	95 73.1%	96 73.8%	96 74.4%	107 82.3%	85 65.4%	85 65.9%	92 70.8%	93 71.5%	1096 70.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	23 17.8%	19 14.8%	29 22.5%	26 20%	20 15.4%	22 16.9%	17 13.2%	15 11.5%	28 21.5%	23 17.8%	21 16.2%	22 16.9%	265 17.1%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	83.38 (18.378)	84.63 (19.378)	83.25 (18.326)	84.68 (18.634)	85.95 (18.498)	82.90 (16.570)	85.86 (20.347)	83.68 (18.340)	85.77 (18.844)	82.10 (17.019)	85.01 (18.536)	82.79 (18.768)	84.17 (18.470)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.48 (10.157)	164.61 (10.614)	162.38 (9.790)	164.25 (11.007)	164.59 (10.841)	163.74 (10.456)	164.59 (9.724)	163.63 (11.036)	163.64 (9.548)	163.14 (10.961)	163.82 (10.708)	163.73 (11.432)	163.88 (10.522)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.59 (4.808)	30.96 (5.133)	31.48 (5.733)	31.25 (5.280)	31.53 (4.979)	30.78 (4.723)	31.41 (5.391)	31.09 (5.054)	31.86 (5.585)	30.69 (4.721)	31.51 (5.206)	30.62 (4.751)	31.15 (5.122)
Diabetes Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.01 (4.958)	6.17 (5.614)	5.55 (4.879)	5.70 (4.767)	6.08 (5.485)	6.86 (5.489)	7.63 (7.069)	5.81 (5.054)	6.63 (6.005)	5.68 (4.232)	6.59 (5.273)	6.22 (5.014)	6.24 (5.375)
Baseline metformin dose (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	1936.8 (428.41)	1902.0 (450.17)	1851.2 (413.85)	1892.6 (410.70)	1909.6 (418.98)	1880.0 (413.65)	1853.5 (435.72)	1822.3 (444.22)	1867.1 (455.48)	1918.6 (417.91)	1919.6 (421.22)	1884.6 (439.47)	1886.5 (429.08)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)
Description	The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg). This combination group includes participants from the following three treatment arms: Placebo + Pioglitazone 15 mg Placebo + Pioglitazone 30 mg Placebo + Pioglitazone 45 mg	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg). This combination group includes participants from the following three treatment arms: Alogliptin 12.5 mg + Pioglitazone 15 mg Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 45 mg	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg). This combination group includes participants from the following three treatment arms: Alogliptin 25 mg + Pioglitazone 15 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 45 mg
Measure Participants	376	385	377
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.89 (0.046)	-1.43 (0.046)	-1.42 (0.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone Alone, Alogliptin 12.5 + Pioglitazone
	Comments	The null hypothesis was that the doses of alogliptin do not have any additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone. The alternative hypothesis was that at least the higher dose of alogliptin would have an additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	For the primary analysis, the overall average HbA1c response of the Alogliptin/pioglitazone combination groups was compared with that of the pioglitazone alone groups at the 2-sided 0.05 significance level with no adjustment for multiple comparisons.
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95% -0.67 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone Alone, Alogliptin 25 + Pioglitazone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95% -0.66 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c Over Time (Grouped Analysis)
Description	The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16 and 20.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=345, 359, 346)	-0.32 (0.023)	-0.57 (0.023)	-0.61 (0.023)
Week 8 (n=376, 385, 377)	-0.61 (0.034)	-1.06 (0.033)	-1.09 (0.034)
Week 12 (n=376, 385, 377)	-0.81 (0.039)	-1.29 (0.039)	-1.38 (0.039)
Week 16 (n=376, 385, 377)	-0.92 (0.041)	-1.44 (0.041)	-1.49 (0.041)
Week 20 (n=376, 385, 377)	-0.92 (0.043)	-1.46 (0.042)	-1.51 (0.043)

3. Secondary Outcome

Title	Change From Baseline to Week 4 in HbA1c
Description	The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	114	110	114	120	116	116	122	118	115	117	112
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.22 (0.039)	-0.46 (0.040)	-0.51 (0.041)	-0.32 (0.040)	-0.53 (0.039)	-0.61 (0.040)	-0.24 (0.040)	-0.60 (0.039)	-0.60 (0.039)	-0.40 (0.040)	-0.58 (0.040)	-0.63 (0.040)

4. Secondary Outcome

Title	Change From Baseline to Week 8 in HbA1c
Description	The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 mg + Pioglitazone 30 mg	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45 mg	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	126	122	123	127	130	127	123	128	124	126	127	126
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.30 (0.058)	-0.75 (0.059)	-0.80 (0.059)	-0.50 (0.058)	-1.01 (0.058)	-1.04 (0.058)	-0.57 (0.059)	-1.05 (0.058)	-1.02 (0.059)	-0.76 (0.058)	-1.11 (0.058)	-1.20 (0.058)

5. Secondary Outcome

Title	Change From Baseline to Week 12 in HbA1c
Description	The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 mg + Pioglitazone 30 mg	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45 mg	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	126	122	123	127	130	127	123	128	124	126	127	126
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.28 (0.067)	-0.84 (0.069)	-0.92 (0.068)	-0.65 (0.067)	-1.24 (0.066)	-1.26 (0.067)	-0.77 (0.068)	-1.29 (0.067)	-1.33 (0.068)	-1.02 (0.067)	-1.34 (0.067)	-1.53 (0.067)

6. Secondary Outcome

Title	Change From Baseline to Week 16 in HbA1c
Description	The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward (LOCF) imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 mg + Pioglitazone 30 mg	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45 mg	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	126	122	123	127	130	127	123	128	124	126	127	126
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.27 (0.071)	-0.82 (0.072)	-1.03 (0.072)	-0.74 (0.071)	-1.36 (0.070)	-1.36 (0.071)	-0.91 (0.072)	-1.42 (0.071)	-1.45 (0.072)	-1.12 (0.071)	-1.53 (0.071)	-1.66 (0.071)

7. Secondary Outcome

Title	Change From Baseline to Week 20 in HbA1c
Description	The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 mg + Pioglitazone 30 mg	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45 mg	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	126	122	123	127	130	127	123	128	124	126	127	126
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.24 (0.074)	-0.75 (0.075)	-0.99 (0.075)	-0.75 (0.074)	-1.39 (0.073)	-1.37 (0.074)	-0.90 (0.075)	-1.43 (0.074)	-1.49 (0.075)	-1.10 (0.074)	-1.57 (0.074)	-1.66 (0.074)

8. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis)
Description	The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 1 (n=358, 355, 354)	-4.1 (1.56)	-22.6 (1.57)	-23.1 (1.57)
Week 2 (n=379, 383, 381)	-11.3 (1.62)	-30.3 (1.61)	-31.6 (1.62)
Week 4 (n=381, 386, 383)	-19.9 (1.67)	-36.8 (1.66)	-39.8 (1.67)
Week 8 (n=381, 386, 383)	-27.3 (1.77)	-42.3 (1.76)	-45.2 (1.77)
Week 12 (n=381, 386, 383)	-30.3 (1.84)	-45.0 (1.83)	-47.6 (1.83)
Week 16 (n=381, 386, 383)	-27.9 (1.86)	-43.7 (1.85)	-45.4 (1.86)
Week 20 (n=381, 386, 383)	-28.1 (2.00)	-43.6 (1.99)	-45.0 (1.99)
Week 26 (n=381, 386, 383)	-28.3 (2.03)	-45.2 (2.02)	-44.2 (2.03)

9. Secondary Outcome

Title	Change From Baseline to Week 1 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 1

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	123	114	117	120	121	123	117	119	118	121	115	113
Least Squares Mean (Standard Error) [mg/dL]	1.8 (2.67)	-14.5 (2.77)	-18.6 (2.73)	-6.1 (2.70)	-21.3 (2.69)	-20.9 (2.66)	0.4 (2.73)	-23.2 (2.71)	-23.2 (2.72)	-6.7 (2.69)	-23.2 (2.76)	-25.0 (2.78)

10. Secondary Outcome

Title	Change From Baseline to Week 2 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 2

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	120	125	127	127	129	124	128	126	128	128	126
Least Squares Mean (Standard Error) [mg/dL]	4.8 (2.78)	-21.9 (2.88)	-18.9 (2.82)	-10.4 (2.80)	-30.1 (2.80)	-31.7 (2.78)	-4.3 (2.83)	-30.0 (2.79)	-31.3 (2.81)	-19.3 (2.79)	-30.8 (2.79)	-31.7 (2.81)

11. Secondary Outcome

Title	Change From Baseline to Week 4 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	125	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	3.8 (2.87)	-20.4 (2.95)	-22.8 (2.92)	-20.2 (2.90)	-35.3 (2.87)	-37.3 (2.86)	-13.4 (2.92)	-37.4 (2.88)	-36.0 (2.91)	-26.1 (2.87)	-37.8 (2.89)	-46.2 (2.89)

12. Secondary Outcome

Title	Change From Baseline to Week 8 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	5.7 (3.05)	-19.5 (3.14)	-19.3 (3.09)	-22.2 (3.07)	-42.3 (3.05)	-39.3 (3.04)	-24.0 (3.10)	-40.5 (3.05)	-44.1 (3.08)	-35.6 (3.05)	-44.0 (3.06)	-52.3 (3.07)

13. Secondary Outcome

Title	Change From Baseline to Week 12 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	3.4 (3.16)	-19.3 (3.25)	-23.3 (3.19)	-23.0 (3.18)	-42.9 (3.16)	-42.5 (3.14)	-26.6 (3.21)	-42.8 (3.16)	-49.0 (3.19)	-41.3 (3.16)	-49.2 (3.17)	-51.4 (3.18)

14. Secondary Outcome

Title	Change From Baseline to Week 16 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	1.4 (3.20)	-16.2 (3.29)	-22.6 (3.24)	-21.2 (3.22)	-41.6 (3.20)	-39.1 (3.19)	-26.3 (3.25)	-41.5 (3.20)	-43.4 (3.24)	-36.3 (3.20)	-47.9 (3.21)	-53.8 (3.22)

15. Secondary Outcome

Title	Change From Baseline to Week 20 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	6.7 (3.43)	-8.7 (3.53)	-23.5 (3.48)	-22.4 (3.46)	-43.0 (3.43)	-39.3 (3.42)	-26.3 (3.49)	-41.1 (3.44)	-43.1 (3.47)	-35.7 (3.43)	-46.8 (3.45)	-52.4 (3.46)

16. Secondary Outcome

Title	Change From Baseline to Week 26 in Fasting Plasma Glucose
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	126	129	128	127
Least Squares Mean (Standard Error) [mg/dL]	6.5 (3.50)	-13.2 (3.59)	-18.6 (3.54)	-23.6 (3.52)	-42.0 (3.50)	-38.0 (3.48)	-28.8 (3.55)	-42.2 (3.50)	-41.7 (3.54)	-32.4 (3.49)	-51.3 (3.51)	-52.7 (3.52)

17. Secondary Outcome

Title	Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)
Description	Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L). This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	From Week 1 to Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	381	386	384
Number [percentage of participants]	39.4 30.5%	24.6 19.2%	22.1 17.1%

18. Secondary Outcome

Title	Percentage of Participants With Marked Hyperglycemia
Description	Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
Time Frame	From Week 1 to Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	122	126	127	129	130	125	129	127	129	128	127
Number [percentage of participants]	60.5 46.9%	42.6 33.3%	39.7 30.8%	37.8 29.1%	27.1 20.8%	22.3 17.2%	39.2 30.4%	26.4 20.3%	23.6 18.2%	41.1 31.9%	20.3 15.6%	20.5 15.8%

19. Secondary Outcome

Title	Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)
Description	Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time Frame	From Week 1 to Week 26.

Outcome Measure Data

Analysis Population Description
Full analysis set including patients with at least 1 postbaseline visit. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	376	382	377
Number [percentage of participants]	11.4 8.8%	3.9 3%	3.4 2.6%

20. Secondary Outcome

Title	Percentage of Participants Meeting Rescue Criteria
Description	Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory: After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL; From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL; From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL; From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time Frame	From Week 1 to Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set including patients with at least 1 postbaseline visit.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	124	125	127	129	129	123	126	123	126	127	125
Number [percentage of participants]	32.8 25.4%	14.5 11.3%	12.8 9.9%	10.2 7.8%	4.7 3.6%	3.9 3%	15.4 11.9%	4.8 3.7%	4.9 3.8%	8.7 6.7%	2.4 1.8%	1.6 1.2%

21. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	12.4 9.6%	27.9 21.8%	29.2 22.6%

22. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	0.8 0.6%	8.6 6.7%	12.4 9.6%	6.2 4.8%	21.5 16.5%	24.6 18.9%	11.6 9%	30.0 23.1%	30.0 23.1%	19.4 15%	32.3 24.8%	33.1 25.5%

23. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	30.5 23.6%	54.6 42.7%	55.9 43.3%

24. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 7%
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	6.2 4.8%	22.7 17.7%	27.1 21%	25.6 19.7%	49.2 37.8%	54.6 42%	29.5 22.9%	53.1 40.8%	53.1 40.8%	36.4 28.2%	61.5 47.3%	60.0 46.2%

25. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	54.8 42.5%	77.4 60.5%	74.1 57.4%

26. Secondary Outcome

Title	Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Description	Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	24.8 19.2%	38.3 29.9%	55.0 42.6%	51.9 39.9%	77.7 59.8%	71.5 55%	55.8 43.3%	73.8 56.8%	72.3 55.6%	56.6 43.9%	80.8 62.2%	78.5 60.4%

27. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	67.2 52.1%	85.6 66.9%	83.3 64.6%

28. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	31.8 24.7%	57.8 45.2%	66.7 51.7%	61.2 47.1%	86.2 66.3%	79.2 60.9%	68.2 52.9%	86.9 66.8%	83.8 64.5%	72.1 55.9%	83.8 64.5%	86.9 66.8%

29. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	45.7 35.4%	71.8 56.1%	69.5 53.9%

30. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	16.3 12.6%	33.6 26.3%	47.3 36.7%	36.4 28%	69.2 53.2%	66.9 51.5%	46.5 36%	73.1 56.2%	69.2 53.2%	54.3 42.1%	73.1 56.2%	72.3 55.6%

31. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	27.6 21.4%	45.9 35.9%	50.3 39%

32. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	5.4 4.2%	15.6 12.2%	28.7 22.2%	21.7 16.7%	41.5 31.9%	46.2 35.5%	27.1 21%	45.4 34.9%	46.2 35.5%	34.1 26.4%	50.8 39.1%	58.5 45%

33. Primary Outcome

Title	Change From Baseline to Week 26 in HbA1c
Description	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

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	126	122	123	127	130	127	123	128	124	126	127	126
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.13 (0.080)	-0.64 (0.081)	-0.90 (0.081)	-0.75 (0.079)	-1.34 (0.078)	-1.27 (0.079)	-0.92 (0.081)	-1.39 (0.079)	-1.39 (0.080)	-1.00 (0.080)	-1.55 (0.079)	-1.60 (0.080)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 12.5 + Pioglitazone, Alogliptin 12.5 + Pioglitazone 15
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	As a supportive analysis, each of the individual combination treatment groups was compared with the component treatment groups receiving aloliptin alone and pioglitazone alone at the 2-sided 0.05 significance level with no multiplicity adjustment.
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95% -0.93 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 15, Alogliptin 12.5 + Pioglitazone 15
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95% -0.81 to -0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 25 + Pioglitazone, Alogliptin 25 + Pioglitazone 15
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95% -0.59 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 15, Alogliptin 25 + Pioglitazone 15
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95% -0.74 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 12.5 + Pioglitazone, Alogliptin 12.5 + Pioglitazone 30
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95% -0.98 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 30, Alogliptin 12.5 + Pioglitazone 30
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95% -0.70 to -0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 25 + Pioglitazone, Alogliptin 25 + Pioglitazone 30
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95% -0.71 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 30, Alogliptin 25 + Pioglitazone 30
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95% -0.70 to -0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 12.5 + Pioglitazone, Alogliptin 12.5 + Pioglitazone 45
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95% -1.13 to -0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 45, Alogliptin 12.5 + Pioglitazone 45
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95% -0.77 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 25 + Pioglitazone, Alogliptin 25 + Pioglitazone 45
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95% -0.92 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo + Pioglitazone 45, Alogliptin 25 + Pioglitazone 45
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95% -0.83 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Number [percentage of participants]	11.1 8.6%	25.4 19.8%	27.7 21.5%

35. Secondary Outcome

Title	Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%
Description	Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	129	128	129	129	130	130	129	130	130	129	130	130
Number [percentage of participants]	1.6 1.2%	7.8 6.1%	11.6 9%	7.0 5.4%	23.1 17.8%	21.5 16.5%	9.3 7.2%	22.3 17.2%	26.2 20.2%	17.1 13.3%	30.8 23.7%	35.4 27.2%

36. Secondary Outcome

Title	Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis)
Description	Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=328, 319, 327)	-6.2 (0.81)	-10.3 (0.82)	-10.1 (0.81)
Week 8 (n=357, 347, 358)	-7.2 (0.87)	-11.3 (0.88)	-11.3 (0.87)
Week 12 (n=357, 347, 358)	-8.2 (0.91)	-11.6 (0.93)	-11.6 (0.91)
Week 16 (n=358, 348, 358)	-7.2 (0.92)	-12.2 (0.94)	-11.3 (0.92)
Week 20 (n=358, 349, 359)	-6.6 (1.08)	-10.4 (1.09)	-10.7 (1.08)
Week 26 (n=358, 349, 359)	-5.3 (1.09)	-10.6 (1.11)	-9.5 (1.09)

37. Secondary Outcome

Title	Change From Baseline to Week 4 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	116	111	109	107	109	109	110	105	114	111	105	104
Least Squares Mean (Standard Error) [pmol/L]	-0.1 (1.36)	-4.7 (1.39)	-2.3 (1.41)	-4.8 (1.42)	-9.9 (1.41)	-8.9 (1.41)	-6.7 (1.40)	-9.6 (1.43)	-9.5 (1.37)	-7.2 (1.39)	-11.3 (1.43)	-11.7 (1.44)

38. Secondary Outcome

Title	Change From Baseline to Week 8 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	123	121	119	120	116	113	119	120	115	119
Least Squares Mean (Standard Error) [pmol/L]	0.7 (1.48)	0.2 (1.50)	-2.6 (1.48)	-3.8 (1.49)	-11.1 (1.50)	-10.7 (1.50)	-8.8 (1.52)	-11.8 (1.54)	-9.4 (1.50)	-9.0 (1.50)	-11.0 (1.53)	-13.8 (1.50)

39. Secondary Outcome

Title	Change From Baseline to Week 12 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	123	121	119	120	116	113	119	120	115	119
Least Squares Mean (Standard Error) [pmol/L]	-1.0 (1.56)	-0.7 (1.57)	-2.3 (1.56)	-5.3 (1.57)	-10.1 (1.58)	-8.8 (1.58)	-11.2 (1.60)	-12.1 (1.63)	-12.7 (1.58)	-8.1 (1.58)	-12.7 (1.61)	-13.2 (1.58)

40. Secondary Outcome

Title	Change From Baseline to Week 16 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	123	121	120	120	117	113	119	120	115	119
Least Squares Mean (Standard Error) [pmol/L]	-3.0 (1.58)	0.0 (1.60)	-2.3 (1.58)	-3.7 (1.59)	-11.0 (1.60)	-8.4 (1.60)	-10.0 (1.62)	-12.6 (1.65)	-11.2 (1.60)	-8.0 (1.60)	-13.0 (1.63)	-14.4 (1.60)

41. Secondary Outcome

Title	Change From Baseline to Week 20 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	123	121	121	121	117	113	119	120	115	119
Least Squares Mean (Standard Error) [pmol/L]	-0.9 (1.85)	1.5 (1.86)	-3.0 (1.84)	-3.4 (1.86)	-11.2 (1.86)	-8.7 (1.86)	-9.3 (1.89)	-10.0 (1.92)	-10.7 (1.87)	-7.1 (1.86)	-10.2 (1.90)	-12.5 (1.87)

42. Secondary Outcome

Title	Change From Baseline to Week 26 in Fasting Proinsulin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	123	121	121	121	117	113	119	120	115	119
Least Squares Mean (Standard Error) [pmol/L]	1.2 (1.87)	0.7 (1.88)	-3.3 (1.86)	-3.5 (1.88)	-10.9 (1.88)	-7.2 (1.88)	-8.4 (1.91)	-8.9 (1.95)	-8.8 (1.89)	-4.1 (1.89)	-12.1 (1.93)	-12.6 (1.89)

43. Secondary Outcome

Title	Change From Baseline in Insulin Over Time (Grouped Analysis)
Description	The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=325, 318, 326)	-2.29 (0.440)	-2.11 (0.445)	-2.19 (0.440)
Week 8 (n=355, 346, 356)	-2.35 (0.535)	-2.44 (0.542)	-2.36 (0.534)
Week 12 (n=355, 347, 356)	-2.62 (0.498)	-1.73 (0.503)	-2.62 (0.497)
Week 16 (n=356, 348, 356)	-2.19 (0.488)	-2.60 (0.494)	-2.48 (0.488)
Week 20 (n=356, 349, 357)	-2.35 (0.511)	-1.91 (0.516)	-2.06 (0.510)
Week 26 (n=356, 349, 357)	-1.74 (1.212)	-2.05 (1.225)	-1.66 (1.210)

44. Secondary Outcome

Title	Change From Baseline to Week 4 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	116	110	106	107	109	108	109	104	114	109	105	104
Least Squares Mean (Standard Error) [µIU/mL]	1.06 (0.737)	-0.33 (0.756)	2.31 (0.771)	-1.68 (0.767)	-3.03 (0.760)	-1.86 (0.763)	-2.43 (0.760)	-1.45 (0.779)	-2.05 (0.743)	-2.76 (0.760)	-1.85 (0.774)	-2.65 (0.778)

45. Secondary Outcome

Title	Change From Baseline to Week 8 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	119	119	116	112	118	118	115	119
Least Squares Mean (Standard Error) [µIU/mL]	-0.46 (0.912)	1.80 (0.923)	1.69 (0.909)	-1.47 (0.916)	-2.21 (0.923)	-2.78 (0.923)	-2.74 (0.935)	-3.15 (0.953)	-1.20 (0.927)	-2.83 (0.927)	-1.96 (0.939)	-3.09 (0.924)

46. Secondary Outcome

Title	Change From Baseline to Week 12 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	119	119	116	113	118	118	115	119
Least Squares Mean (Standard Error) [µIU/mL]	0.06 (0.849)	1.79 (0.859)	1.93 (0.846)	-1.29 (0.852)	-1.47 (0.859)	-2.01 (0.859)	-3.61 (0.870)	-1.36 (0.882)	-2.83 (0.863)	-2.95 (0.863)	-2.35 (0.874)	-3.01 (0.859)

47. Secondary Outcome

Title	Change From Baseline to Week 16 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	120	119	117	113	118	118	115	119
Least Squares Mean (Standard Error) [µIU/mL]	0.34 (0.833)	1.22 (0.843)	1.83 (0.830)	-0.63 (0.836)	-2.28 (0.840)	-1.11 (0.843)	-3.46 (0.851)	-2.50 (0.866)	-2.82 (0.847)	-2.48 (0.847)	-3.00 (0.858)	-3.52 (0.844)

48. Secondary Outcome

Title	Change From Baseline to Week 20 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	121	120	117	113	118	118	115	119
Least Squares Mean (Standard Error) [µIU/mL]	0.18 (0.873)	2.03 (0.883)	0.76 (0.869)	-0.66 (0.876)	-2.35 (0.876)	-0.90 (0.880)	-3.29 (0.891)	-2.20 (0.907)	-2.29 (0.887)	-3.12 (0.887)	-1.16 (0.899)	-3.01 (0.884)

49. Secondary Outcome

Title	Change From Baseline to Week 26 in Insulin Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	121	120	117	113	118	118	115	119
Least Squares Mean (Standard Error) [µIU/mL]	6.78 (2.071)	1.33 (2.096)	1.43 (2.063)	-0.78 (2.078)	-3.05 (2.078)	-0.76 (2.087)	-2.56 (2.114)	-0.76 (2.152)	-1.42 (2.105)	-1.88 (2.105)	-2.33 (2.132)	-2.79 (2.096)

50. Secondary Outcome

Title	Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis)
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=325, 315, 326)	-0.021 (0.0088)	-0.078 (0.0089)	-0.057 (0.0088)
Week 8 (n=355, 344, 356)	-0.019 (0.0084)	-0.079 (0.0086)	-0.081 (0.0084)
Week 12 (n=355, 345, 356)	-0.042 (0.0083)	-0.086 (0.0084)	-0.082 (0.0083)
Week 16 (n=356, 346, 356)	-0.033 (0.0077)	-0.091 (0.0078)	-0.077 (0.0077)
Week 20 (n=356, 347, 357)	-0.034 (0.0076)	-0.088 (0.0077)	-0.078 (0.0076)
Week 26 (n=356, 347, 357)	-0.027 (0.0088)	-0.087 (0.0090)	-0.076 (0.0088)

51. Secondary Outcome

Title	Change From Baseline to Week 4 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	116	110	106	107	108	108	109	102	114	109	105	104
Least Squares Mean (Standard Error) [ratio]	-0.015 (0.0147)	-0.039 (0.0151)	-0.058 (0.0154)	-0.029 (0.0153)	-0.054 (0.0153)	-0.054 (0.0153)	-0.023 (0.0152)	-0.068 (0.0157)	-0.045 (0.0149)	-0.009 (0.0152)	-0.111 (0.0155)	-0.072 (0.0156)

52. Secondary Outcome

Title	Change From Baseline to Week 8 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	119	119	116	110	118	118	115	119
Least Squares Mean (Standard Error) [ratio]	0.005 (0.0144)	-0.025 (0.0146)	-0.045 (0.0143)	-0.007 (0.0144)	-0.086 (0.0146)	-0.077 (0.0146)	-0.036 (0.0148)	-0.054 (0.0152)	-0.072 (0.0146)	-0.013 (0.0146)	-0.098 (0.0148)	-0.093 (0.0146)

53. Secondary Outcome

Title	Change From Baseline to Week 12 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	119	119	116	111	118	118	115	119
Least Squares Mean (Standard Error) [ratio]	-0.006 (0.0142)	-0.024 (0.0144)	-0.041 (0.0141)	-0.041 (0.0142)	-0.073 (0.0144)	-0.056 (0.0144)	-0.063 (0.0146)	-0.072 (0.0149)	-0.088 (0.0144)	-0.021 (0.0144)	-0.112 (0.0146)	-0.101 (0.0144)

54. Secondary Outcome

Title	Change From Baseline to Week 16 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	120	119	117	111	118	118	115	119
Least Squares Mean (Standard Error) [ratio]	-0.026 (0.0132)	-0.036 (0.0133)	-0.046 (0.0131)	-0.035 (0.0132)	-0.078 (0.0133)	-0.066 (0.0134)	-0.035 (0.0135)	-0.094 (0.0138)	-0.061 (0.0134)	-0.030 (0.0134)	-0.102 (0.0136)	-0.104 (0.0133)

55. Secondary Outcome

Title	Change From Baseline to Week 20 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	121	120	117	111	118	118	115	119
Least Squares Mean (Standard Error) [ratio]	-0.007 (0.0131)	-0.014 (0.0132)	-0.046 (0.0130)	-0.039 (0.0131)	-0.081 (0.0131)	-0.065 (0.0132)	-0.042 (0.0133)	-0.085 (0.0137)	-0.077 (0.0133)	-0.020 (0.0133)	-0.099 (0.0134)	-0.092 (0.0132)

56. Secondary Outcome

Title	Change From Baseline to Week 26 in Proinsulin/Insulin Ratio
Description	The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL). Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	119	123	121	121	120	117	111	118	118	115	119
Least Squares Mean (Standard Error) [ratio]	-0.007 (0.0151)	-0.001 (0.0153)	-0.064 (0.0151)	-0.038 (0.0152)	-0.071 (0.0152)	-0.063 (0.0152)	-0.030 (0.0154)	-0.081 (0.0159)	-0.072 (0.0154)	-0.014 (0.0154)	-0.109 (0.0156)	-0.092 (0.0153)

57. Secondary Outcome

Title	Change From Baseline in C-peptide Over Time (Grouped Analysis)
Description	C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=335, 335, 336)	-0.292 (0.0417)	-0.255 (0.0417)	-0.282 (0.0416)
Week 8 (n=367, 366, 371)	-0.356 (0.0464)	-0.327 (0.0464)	-0.311 (0.0461)
Week 12 (n=367, 369, 374)	-0.268 (0.0781)	-0.249 (0.0779)	-0.334 (0.0774)
Week 16 (n=369, 374, 374)	-0.352 (0.0456)	-0.343 (0.0453)	-0.333 (0.0453)
Week 20 (n=369, 375, 375)	-0.360 (0.0465)	-0.350 (0.0461)	-0.293 (0.0461)
Week 26 (n=371, 378, 375)	-0.341 (0.0460)	-0.346 (0.0456)	-0.326 (0.0457)

58. Secondary Outcome

Title	Change From Baseline to Week 4 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	117	110	108	109	114	112	112	113	117	114	108	107
Least Squares Mean (Standard Error) [ng/mL]	0.002 (0.0705)	-0.032 (0.0727)	0.076 (0.0734)	-0.246 (0.0730)	-0.248 (0.0714)	-0.238 (0.0720)	-0.232 (0.0721)	-0.259 (0.0718)	-0.268 (0.0705)	-0.393 (0.0714)	-0.252 (0.0734)	-0.337 (0.0738)

59. Secondary Outcome

Title	Change From Baseline to Week 8 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	124	121	123	124	124	123	119	123	124	124	119	124
Least Squares Mean (Standard Error) [ng/mL]	-0.044 (0.0798)	0.114 (0.0807)	0.108 (0.0801)	-0.221 (0.0798)	-0.315 (0.0798)	-0.261 (0.0801)	-0.380 (0.0814)	-0.365 (0.0802)	-0.207 (0.0797)	-0.467 (0.0798)	-0.300 (0.0814)	-0.464 (0.0798)

60. Secondary Outcome

Title	Change From Baseline to Week 12 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	124	124	125	119	124	124	124	121	125
Least Squares Mean (Standard Error) [ng/mL]	-0.055 (0.1338)	0.083 (0.1360)	0.140 (0.1349)	0.116 (0.1344)	-0.155 (0.1344)	-0.215 (0.1338)	-0.439 (0.1372)	-0.212 (0.1345)	-0.326 (0.1343)	-0.483 (0.1344)	-0.381 (0.1360)	-0.464 (0.1339)

61. Secondary Outcome

Title	Change From Baseline to Week 16 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	124	126	125	121	125	124	124	123	125
Least Squares Mean (Standard Error) [ng/mL]	-0.076 (0.0783)	0.032 (0.0796)	0.101 (0.0789)	-0.242 (0.0786)	-0.282 (0.0780)	-0.184 (0.0783)	-0.410 (0.0796)	-0.318 (0.0783)	-0.306 (0.0786)	-0.404 (0.0786)	-0.431 (0.0789)	-0.510 (0.0783)

62. Secondary Outcome

Title	Change From Baseline to Week 20 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	124	127	126	121	125	124	124	123	125
Least Squares Mean (Standard Error) [ng/mL]	-0.046 (0.0799)	0.114 (0.0812)	0.019 (0.0805)	-0.193 (0.0802)	-0.377 (0.0792)	-0.184 (0.0795)	-0.380 (0.0812)	-0.343 (0.0799)	-0.266 (0.0802)	-0.506 (0.0802)	-0.329 (0.0805)	-0.430 (0.0799)

63. Secondary Outcome

Title	Change From Baseline to Week 26 in C-peptide Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	126	121	126	124	125	124	125
Least Squares Mean (Standard Error) [ng/mL]	-0.011 (0.0793)	0.000 (0.0802)	0.059 (0.0799)	-0.239 (0.0792)	-0.380 (0.0783)	-0.204 (0.0789)	-0.353 (0.0805)	-0.235 (0.0790)	-0.300 (0.0795)	-0.429 (0.0793)	-0.421 (0.0796)	-0.474 (0.0793)

64. Secondary Outcome

Title	Change From Baseline in Total Cholesterol Over Time (Grouped Analysis)
Description	Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=345, 354, 348)	1.6 (1.41)	-4.3 (1.39)	-6.5 (1.40)
Week 8 (n=374, 380, 376)	4.8 (1.42)	-1.8 (1.41)	-3.3 (1.42)
Week 12 (n=374, 380, 376)	6.6 (1.47)	1.3 (1.46)	-1.7 (1.46)
Week 16 (n=374, 380, 376)	6.5 (1.52)	1.2 (1.51)	0.1 (1.51)
Week 20 (n=374, 380, 376)	5.9 (1.56)	3.0 (1.55)	1.5 (1.56)
Week 26 (n=374, 380, 376)	8.0 (1.63)	4.4 (1.61)	3.9 (1.62)

65. Secondary Outcome

Title	Change From Baseline to Week 4 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	112	111	112	117	118	117	121	118	116	116	112
Least Squares Mean (Standard Error) [mg/dL]	1.3 (2.40)	-3.8 (2.47)	-3.7 (2.48)	2.1 (2.47)	-2.3 (2.42)	-10.2 (2.41)	3.7 (2.42)	-7.2 (2.38)	-2.7 (2.41)	-1.2 (2.43)	-3.6 (2.43)	-6.7 (2.47)

66. Secondary Outcome

Title	Change From Baseline to Week 8 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	10.9 (2.46)	-1.4 (2.50)	-0.3 (2.48)	7.3 (2.46)	-2.3 (2.43)	-4.1 (2.44)	6.6 (2.48)	0.1 (2.45)	0.3 (2.47)	0.3 (2.45)	-3.1 (2.46)	-6.2 (2.46)

67. Secondary Outcome

Title	Change From Baseline to Week 12 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	7.8 (2.54)	0.4 (2.57)	0.1 (2.56)	8.7 (2.54)	1.9 (2.51)	-0.2 (2.52)	7.3 (2.56)	0.3 (2.52)	-1.0 (2.55)	3.7 (2.53)	1.7 (2.54)	-3.9 (2.54)

68. Secondary Outcome

Title	Change From Baseline to Week 16 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	5.0 (2.62)	-0.5 (2.66)	-2.9 (2.65)	7.2 (2.62)	-0.4 (2.59)	3.2 (2.60)	10.0 (2.65)	0.9 (2.61)	-1.2 (2.63)	2.3 (2.61)	2.9 (2.62)	-1.8 (2.62)

69. Secondary Outcome

Title	Change From Baseline to Week 20 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	6.7 (2.70)	1.8 (2.74)	-1.9 (2.73)	6.3 (2.70)	4.0 (2.67)	1.4 (2.68)	7.0 (2.73)	1.1 (2.68)	3.4 (2.71)	4.6 (2.69)	4.0 (2.70)	-0.3 (2.70)

70. Secondary Outcome

Title	Change From Baseline to Week 26 in Total Cholesterol Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	4.4 (2.82)	2.2 (2.85)	0.9 (2.84)	5.8 (2.81)	4.3 (2.78)	3.5 (2.79)	8.8 (2.84)	2.8 (2.80)	3.2 (2.83)	9.5 (2.80)	6.0 (2.81)	5.1 (2.81)

71. Secondary Outcome

Title	Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Description	Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=330, 336, 338)	3.1 (1.23)	-0.5 (1.22)	-1.9 (1.22)
Week 8 (n=365, 365, 365)	5.9 (1.28)	1.3 (1.28)	0.1 (1.28)
Week 12 (n=365, 367, 366)	6.9 (1.29)	3.3 (1.29)	1.5 (1.29)
Week 16 (n=365, 368, 366)	6.1 (1.29)	3.3 (1.29)	2.4 (1.29)
Week 20 (n=365, 368, 366)	6.9 (1.37)	4.2 (1.36)	3.0 (1.37)
Week 26 (n=365, 368, 366)	7.4 (1.39)	5.2 (1.39)	5.6 (1.39)

72. Secondary Outcome

Title	Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	113	102	105	107	112	113	112	115	114	111	109	111
Least Squares Mean (Standard Error) [mg/dL]	2.1 (2.11)	-2.4 (2.22)	1.4 (2.19)	2.6 (2.16)	1.6 (2.12)	-2.7 (2.11)	3.2 (2.12)	-2.8 (2.09)	0.4 (2.10)	3.4 (2.13)	-0.3 (2.15)	-3.4 (2.13)

73. Secondary Outcome

Title	Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	119	122	123	122	120	123	119	123	119	124
Least Squares Mean (Standard Error) [mg/dL]	9.4 (2.24)	2.1 (2.30)	3.4 (2.24)	7.3 (2.21)	-0.4 (2.21)	1.0 (2.21)	5.4 (2.24)	2.4 (2.21)	2.7 (2.24)	4.8 (2.21)	2.0 (2.24)	-3.2 (2.20)

74. Secondary Outcome

Title	Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	115	119	122	125	122	120	123	120	123	119	124
Least Squares Mean (Standard Error) [mg/dL]	6.5 (2.26)	1.9 (2.30)	3.7 (2.26)	8.9 (2.24)	3.3 (2.21)	3.8 (2.24)	6.1 (2.26)	1.9 (2.23)	0.9 (2.25)	5.7 (2.23)	4.9 (2.26)	-0.3 (2.22)

75. Secondary Outcome

Title	Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	116	119	122	125	122	120	123	120	123	120	124
Least Squares Mean (Standard Error) [mg/dL]	4.2 (2.25)	1.3 (2.29)	0.9 (2.26)	7.1 (2.23)	2.9 (2.21)	4.6 (2.23)	7.1 (2.25)	2.1 (2.23)	0.8 (2.25)	4.1 (2.22)	4.9 (2.25)	1.8 (2.21)

76. Secondary Outcome

Title	Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	116	119	122	125	122	120	123	120	123	120	124
Least Squares Mean (Standard Error) [mg/dL]	6.9 (2.39)	2.9 (2.43)	1.9 (2.40)	7.7 (2.37)	4.3 (2.34)	3.0 (2.37)	6.6 (2.39)	2.3 (2.36)	4.1 (2.39)	6.3 (2.36)	6.1 (2.39)	1.9 (2.35)

77. Secondary Outcome

Title	Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	116	119	122	125	122	120	123	120	123	120	124
Least Squares Mean (Standard Error) [mg/dL]	3.6 (2.43)	2.8 (2.47)	3.6 (2.44)	7.9 (2.41)	3.7 (2.38)	6.1 (2.41)	6.2 (2.43)	2.9 (2.40)	3.0 (2.43)	8.1 (2.40)	9.1 (2.43)	7.7 (2.39)

78. Secondary Outcome

Title	Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis)
Description	Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=345, 353, 348)	3.0 (0.33)	2.7 (0.33)	3.4 (0.33)
Week 8 (n=374, 380, 376)	4.0 (0.35)	4.1 (0.34)	4.6 (0.35)
Week 12 (n=374, 380, 376)	5.4 (0.37)	5.3 (0.37)	5.1 (0.37)
Week 16 (n=374, 380, 376)	5.2 (0.39)	5.2 (0.38)	5.0 (0.38)
Week 20 (n=374, 380, 376)	5.2 (0.40)	5.7 (0.40)	5.2 (0.40)
Week 26 (n=374, 380, 376)	5.1 (0.41)	5.5 (0.41)	5.0 (0.41)

79. Secondary Outcome

Title	Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	112	111	112	116	118	117	121	118	116	116	112
Least Squares Mean (Standard Error) [mg/dL]	-0.4 (0.57)	-0.6 (0.59)	-0.5 (0.59)	2.5 (0.59)	1.6 (0.58)	1.6 (0.57)	3.2 (0.57)	2.3 (0.56)	3.5 (0.57)	3.3 (0.58)	4.2 (0.58)	5.1 (0.59)

80. Secondary Outcome

Title	Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	-0.5 (0.60)	-0.1 (0.61)	0.6 (0.61)	2.8 (0.60)	2.3 (0.59)	2.9 (0.60)	4.8 (0.61)	4.2 (0.60)	4.6 (0.60)	4.5 (0.60)	5.7 (0.60)	6.3 (0.60)

81. Secondary Outcome

Title	Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	-0.2 (0.64)	0.0 (0.65)	0.3 (0.64)	3.8 (0.64)	3.7 (0.63)	3.7 (0.63)	6.3 (0.64)	5.8 (0.63)	5.3 (0.64)	6.1 (0.63)	6.3 (0.64)	6.4 (0.64)

82. Secondary Outcome

Title	Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	-0.3 (0.67)	0.4 (0.68)	0.7 (0.67)	3.9 (0.67)	4.2 (0.66)	4.0 (0.66)	5.7 (0.67)	5.5 (0.66)	4.3 (0.67)	5.9 (0.66)	6.1 (0.67)	6.7 (0.67)

83. Secondary Outcome

Title	Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	0.6 (0.70)	0.9 (0.71)	0.5 (0.70)	3.8 (0.70)	4.3 (0.69)	3.9 (0.69)	5.9 (0.70)	5.7 (0.69)	5.3 (0.70)	5.9 (0.70)	7.1 (0.70)	6.5 (0.70)

84. Secondary Outcome

Title	Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	0.5 (0.71)	0.6 (0.72)	1.3 (0.71)	3.8 (0.71)	4.2 (0.70)	4.1 (0.70)	5.5 (0.71)	6.0 (0.70)	5.0 (0.71)	6.1 (0.70)	6.2 (0.71)	6.0 (0.71)

85. Secondary Outcome

Title	Change From Baseline in Triglycerides Over Time (Grouped Analysis)
Description	Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 4 (n=345, 354, 348)	-31.5 (4.07)	-38.9 (4.02)	-48.0 (4.06)
Week 8 (n=374, 380, 376)	-34.7 (4.37)	-44.4 (4.34)	-47.9 (4.36)
Week 12 (n=374, 380, 376)	-34.5 (4.25)	-47.5 (4.21)	-49.4 (4.24)
Week 16 (n=374, 380, 376)	-29.4 (4.43)	-49.3 (4.39)	-46.3 (4.42)
Week 20 (n=374, 380, 376)	-34.9 (4.30)	-43.6 (4.27)	-42.7 (4.29)
Week 26 (n=374, 380, 376)	-29.6 (4.42)	-41.4 (4.39)	-40.7 (4.41)

86. Secondary Outcome

Title	Change From Baseline to Week 4 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	112	111	112	117	118	117	121	118	116	116	112
Least Squares Mean (Standard Error) [mg/dL]	-2.4 (6.93)	-2.2 (7.15)	-25.0 (7.18)	-21.5 (7.14)	-35.8 (6.99)	-51.1 (6.96)	-26.7 (6.99)	-42.2 (6.88)	-44.4 (6.96)	-47.1 (7.02)	-39.2 (7.03)	-49.1 (7.15)

87. Secondary Outcome

Title	Change From Baseline to Week 8 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	121	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	26.3 (7.56)	-16.4 (7.69)	-23.0 (7.62)	-20.5 (7.56)	-30.1 (7.47)	-46.4 (7.50)	-30.3 (7.62)	-43.1 (7.51)	-44.5 (7.60)	-53.1 (7.53)	-60.1 (7.57)	-52.7 (7.56)

88. Secondary Outcome

Title	Change From Baseline to Week 12 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	18.9 (7.35)	-4.3 (7.44)	-18.1 (7.41)	-24.1 (7.34)	-37.4 (7.26)	-44.0 (7.29)	-37.4 (7.40)	-47.9 (7.29)	-46.8 (7.38)	-42.1 (7.31)	-57.1 (7.35)	-57.4 (7.35)

89. Secondary Outcome

Title	Change From Baseline to Week 16 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	10.6 (7.66)	-7.5 (7.75)	-26.8 (7.72)	-10.5 (7.66)	-53.0 (7.57)	-33.8 (7.60)	-28.2 (7.72)	-44.2 (7.60)	-45.9 (7.69)	-49.4 (7.63)	-50.7 (7.66)	-59.1 (7.66)

90. Secondary Outcome

Title	Change From Baseline to Week 20 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	5.7 (7.44)	-7.0 (7.53)	-23.7 (7.50)	-18.0 (7.44)	-41.2 (7.35)	-34.6 (7.38)	-37.5 (7.50)	-43.1 (7.39)	-42.4 (7.47)	-49.3 (7.41)	-46.4 (7.44)	-51.2 (7.44)

91. Secondary Outcome

Title	Change From Baseline to Week 26 in Triglyceride Levels
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	125	122	123	125	128	127	123	127	124	126	125	125
Least Squares Mean (Standard Error) [mg/dL]	3.7 (7.65)	-1.1 (7.74)	-15.2 (7.71)	-29.5 (7.65)	-37.7 (7.56)	-38.5 (7.59)	-27.0 (7.71)	-37.3 (7.59)	-33.5 (7.68)	-32.4 (7.62)	-49.3 (7.65)	-50.1 (7.65)

92. Secondary Outcome

Title	Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis)
Description	Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=339, 356, 352)	-0.0707 (0.01483)	-0.1306 (0.01447)	-0.1273 (0.01455)
Week 26 (n=353, 368, 363)	-0.0676 (0.01050)	-0.0945 (0.01029)	-0.1144 (0.01036)

93. Secondary Outcome

Title	Change From Baseline to Week 12 in Free Fatty Acids
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	116	116	115	119	118	111	118	116	113	119	118
Least Squares Mean (Standard Error) [mmol/L]	0.0067 (0.02493)	-0.0149 (0.02535)	-0.0769 (0.02535)	-0.0879 (0.02547)	-0.1305 (0.02502)	-0.1291 (0.02512)	-0.0395 (0.02592)	-0.1167 (0.02515)	-0.1126 (0.02534)	-0.0848 (0.02567)	-0.1447 (0.02503)	-0.1401 (0.02514)

94. Secondary Outcome

Title	Change From Baseline to Week 26 in Free Fatty Acids
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	122	117	124	121	118	122	120	118	122	122
Least Squares Mean (Standard Error) [mmol/L]	-0.0387 (0.01788)	-0.0427 (0.01802)	-0.0386 (0.01787)	-0.0561 (0.01825)	-0.0752 (0.01772)	-0.0972 (0.01793)	-0.0737 (0.01817)	-0.0956 (0.01788)	-0.1232 (0.01801)	-0.0730 (0.01816)	-0.1125 (0.01787)	-0.1228 (0.01787)

95. Secondary Outcome

Title	Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis)
Description	Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=311, 333, 328)	-4.14 (1.970)	-8.76 (1.900)	-8.57 (1.914)
Week 26 (n=341, 354, 348)	-4.56 (2.049)	-2.69 (2.010)	-9.25 (2.027)

96. Secondary Outcome

Title	Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	106	107	107	108	113	109	107	108	109	96	112	110
Least Squares Mean (Standard Error) [ng/mL]	-4.55 (3.367)	3.54 (3.350)	-1.80 (3.353)	-5.32 (3.340)	-6.28 (3.260)	-10.94 (3.320)	-8.53 (3.353)	-10.47 (3.336)	-1.71 (3.321)	1.85 (3.539)	-9.13 (3.277)	-12.63 (3.306)

97. Secondary Outcome

Title	Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	115	114	118	115	119	116	117	116	115	109	119	117
Least Squares Mean (Standard Error) [ng/mL]	-3.00 (3.526)	0.57 (3.540)	-3.29 (3.481)	-5.43 (3.529)	-4.75 (3.465)	-9.62 (3.510)	-5.24 (3.495)	1.89 (3.511)	-6.66 (3.525)	-3.02 (3.622)	-5.22 (3.466)	-11.48 (3.496)

98. Secondary Outcome

Title	Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis)
Description	Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=346, 356, 355)	-2.0274 (0.32717)	-2.4653 (0.32225)	-1.9208 (0.32253)
Week 26 (n=359, 369, 363)	-0.8889 (0.46384)	-1.7716 (0.45715)	-0.9977 (0.46059)

99. Secondary Outcome

Title	Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	114	118	114	119	118	118	119	116	114	118	121
Least Squares Mean (Standard Error) [mg/L]	-1.1053 (0.55528)	-1.0730 (0.56942)	0.3516 (0.55954)	-0.9166 (0.56902)	-2.2362 (0.55706)	-2.4217 (0.55929)	-2.7023 (0.55971)	-2.2143 (0.55757)	-1.0006 (0.56412)	-2.4212 (0.57137)	-2.9032 (0.55979)	-2.2978 (0.55243)

100. Secondary Outcome

Title	Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	121	120	122	119	124	122	121	123	119	119	122	122
Least Squares Mean (Standard Error) [mg/L]	-0.0550 (0.79868)	-0.6606 (0.80145)	0.2618 (0.79488)	0.2375 (0.80439)	-1.2490 (0.78817)	-0.9438 (0.79442)	-1.0480 (0.79805)	-1.1725 (0.79206)	0.1697 (0.80434)	-1.8562 (0.80771)	-2.8933 (0.79515)	-2.2191 (0.79450)

101. Secondary Outcome

Title	Change From Baseline in Adiponectin Over Time (Grouped Analysis)
Description	Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=339, 357, 348)	6.03 (0.353)	6.51 (0.344)	6.51 (0.348)
Week 26 (n=356, 369, 361)	5.98 (0.396)	6.43 (0.388)	6.46 (0.393)

102. Secondary Outcome

Title	Change From Baseline to Week 12 in Adiponectin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	114	115	116	121	117	111	118	114	112	118	117
Least Squares Mean (Standard Error) [μg/mL]	0.02 (0.593)	0.44 (0.609)	0.22 (0.606)	3.54 (0.604)	3.78 (0.591)	2.91 (0.601)	6.07 (0.617)	6.31 (0.599)	7.13 (0.609)	8.47 (0.614)	9.42 (0.598)	9.46 (0.601)

103. Secondary Outcome

Title	Change From Baseline to Week 26 in Adiponectin
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	120	121	119	126	121	118	122	119	119	121	121
Least Squares Mean (Standard Error) [μg/mL]	0.43 (0.676)	0.48 (0.681)	0.26 (0.678)	3.30 (0.685)	4.80 (0.664)	2.93 (0.678)	5.90 (0.687)	6.30 (0.676)	6.87 (0.684)	8.75 (0.684)	8.18 (0.678)	9.59 (0.678)

104. Secondary Outcome

Title	Change From Baseline in Body Weight Over Time (Grouped Analysis)
Description	Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time Frame	Baseline and Weeks 8, 12, 20 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 8 (n=361, 372, 367)	0.45 (0.103)	0.34 (0.101)	0.63 (0.102)
Week 12 (n=368, 374, 373)	0.56 (0.125)	0.57 (0.124)	0.82 (0.124)
Week 20 (n=368, 374, 373)	1.21 (0.152)	1.45 (0.151)	1.46 (0.151)
Week 26 (n=368, 374, 373)	1.49 (0.168)	1.81 (0.167)	1.87 (0.167)

105. Secondary Outcome

Title	Change From Baseline to Week 8 in Body Weight
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	123	119	120	121	126	122	121	125	121	119	121	124
Least Squares Mean (Standard Error) [kg]	-0.13 (0.176)	-0.05 (0.179)	-0.45 (0.178)	0.32 (0.177)	0.09 (0.174)	0.22 (0.176)	0.57 (0.177)	0.49 (0.174)	0.74 (0.177)	0.46 (0.179)	0.43 (0.177)	0.93 (0.175)

106. Secondary Outcome

Title	Change From Baseline to Week 12 in Body Weight
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	123	122	123	122	127	124	122	125	123	124	122	126
Least Squares Mean (Standard Error) [kg]	-0.46 (0.216)	-0.14 (0.217)	-0.56 (0.216)	0.39 (0.217)	0.22 (0.213)	0.39 (0.215)	0.75 (0.217)	0.60 (0.215)	0.98 (0.216)	0.55 (0.216)	0.88 (0.217)	1.08 (0.214)

107. Secondary Outcome

Title	Change From Baseline to Week 20 in Body Weight
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	123	122	123	122	127	124	122	125	123	124	122	126
Least Squares Mean (Standard Error) [kg]	-0.55 (0.263)	-0.08 (0.264)	-0.48 (0.263)	0.76 (0.264)	0.96 (0.259)	0.85 (0.262)	1.51 (0.264)	1.45 (0.261)	1.76 (0.263)	1.35 (0.262)	1.93 (0.264)	1.76 (0.260)

108. Secondary Outcome

Title	Change From Baseline to Week 26 in Body Weight
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	123	122	123	122	127	124	122	125	123	124	122	126
Least Squares Mean (Standard Error) [kg]	-0.66 (0.291)	-0.02 (0.292)	-0.67 (0.291)	0.94 (0.292)	1.25 (0.287)	1.27 (0.290)	1.88 (0.292)	1.89 (0.289)	2.10 (0.291)	1.65 (0.290)	2.30 (0.292)	2.25 (0.288)

109. Secondary Outcome

Title	Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis)
Description	HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=347, 344, 351)	-1.832 (0.3122)	-1.966 (0.3136)	-2.572 (0.3104)
Week 26 (n=348, 346, 352)	-1.571 (0.3501)	-2.209 (0.3512)	-1.711 (0.3481)

110. Secondary Outcome

Title	Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance
Description	The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	117	122	119	117	118	114	113	116	114	114	117
Least Squares Mean (Standard Error) [insulin resistance]	0.337 (0.5333)	0.063 (0.5375)	0.041 (0.5270)	-1.012 (0.5330)	-1.819 (0.5376)	-2.305 (0.5352)	-2.278 (0.5446)	-1.457 (0.5473)	-2.665 (0.5400)	-2.202 (0.5447)	-2.615 (0.5446)	-2.742 (0.5377)

111. Secondary Outcome

Title	Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance
Description	The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	117	122	119	119	119	115	113	116	114	114	117
Least Squares Mean (Standard Error) [insulin resistance]	0.464 (0.5988)	0.311 (0.6036)	-0.179 (0.5918)	-0.864 (0.5985)	-2.300 (0.5986)	-0.223 (0.5985)	-2.061 (0.6089)	-1.871 (0.6147)	-2.056 (0.6064)	-1.789 (0.6117)	-2.456 (0.6116)	-2.854 (0.6038)

112. Secondary Outcome

Title	Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis)
Description	The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=347, 344, 350)	2.591 (3.7892)	23.799 (3.8017)	19.477 (3.7685)
Week 26 (n=348, 346, 351)	5.060 (3.0460)	18.173 (3.0522)	22.182 (3.0297)

113. Secondary Outcome

Title	Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function
Description	The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	118	117	122	119	117	118	114	113	116	114	114	116
Least Squares Mean (Standard Error) [percentage beta cell function]	-3.027 (6.4915)	16.304 (6.5165)	22.996 (6.3854)	2.565 (6.4614)	30.346 (6.5157)	19.887 (6.4916)	1.118 (6.6030)	21.045 (6.6358)	19.935 (6.5444)	4.023 (6.6240)	19.938 (6.6025)	18.541 (6.5456)

114. Secondary Outcome

Title	Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function
Description	The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	118	117	122	119	119	119	115	113	116	114	114	116
Least Squares Mean (Standard Error) [percentage beta cell function]	-0.924 (5.2260)	11.812 (5.2462)	17.814 (5.1407)	2.770 (5.2018)	10.977 (5.2010)	19.320 (5.2044)	8.983 (5.2921)	22.474 (5.3423)	23.475 (5.2687)	3.427 (5.3327)	21.068 (5.3154)	23.752 (5.2696)

115. Secondary Outcome

Title	Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis)
Description	Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=339, 354, 346)	1.4 (1.00)	0.2 (0.98)	0.3 (0.99)
Week 26 (n=354, 367, 356)	-1.6 (1.09)	-1.5 (1.08)	-2.8 (1.09)

116. Secondary Outcome

Title	Change From Baseline to Week 12 in Apolipoprotein A1
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	117	114	112	113	119	114	114	119	118	112	116	114
Least Squares Mean (Standard Error) [mg/dL]	-1.9 (1.70)	-4.4 (1.73)	-3.0 (1.74)	0.8 (1.73)	-1.3 (1.69)	1.7 (1.72)	3.5 (1.72)	0.7 (1.69)	0.4 (1.69)	-0.1 (1.74)	1.1 (1.71)	-1.2 (1.72)

117. Secondary Outcome

Title	Change From Baseline to Week 26 in Apolipoprotein A1
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	118	119	117	125	116	119	122	121	118	120	119
Least Squares Mean (Standard Error) [mg/dL]	-4.9 (1.88)	-3.0 (1.90)	-4.2 (1.89)	-3.3 (1.90)	-3.5 (1.84)	-2.9 (1.91)	-0.2 (1.89)	-0.1 (1.86)	-3.2 (1.87)	-1.4 (1.89)	-1.0 (1.88)	-2.2 (1.89)

118. Secondary Outcome

Title	Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis)
Description	Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=339, 354, 345)	3.1 (0.26)	2.5 (0.26)	2.3 (0.26)
Week 26 (n=354, 367, 355)	2.4 (0.28)	2.1 (0.27)	1.8 (0.28)

119. Secondary Outcome

Title	Change From Baseline to Week 12 in Apolipoprotein A2
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	117	114	112	113	119	114	114	119	117	112	116	114
Least Squares Mean (Standard Error) [mg/dL]	0.4 (0.44)	0.1 (0.45)	0.4 (0.45)	2.4 (0.45)	1.4 (0.44)	1.9 (0.45)	3.7 (0.45)	2.5 (0.44)	1.8 (0.44)	3.0 (0.45)	3.7 (0.45)	3.2 (0.45)

120. Secondary Outcome

Title	Change From Baseline to Week 26 in Apolipoprotein A2
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	118	119	117	125	116	119	122	120	118	120	119
Least Squares Mean (Standard Error) [mg/dL]	0.1 (0.47)	0.2 (0.48)	0.4 (0.48)	1.9 (0.48)	1.2 (0.47)	1.0 (0.48)	2.7 (0.48)	2.1 (0.47)	1.6 (0.47)	2.8 (0.48)	3.1 (0.47)	2.7 (0.48)

121. Secondary Outcome

Title	Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis)
Description	Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=338, 354, 346)	-3.0 (1.09)	-7.9 (1.06)	-10.0 (1.07)
Week 26 (n=354, 367, 356)	-2.8 (1.16)	-6.4 (1.14)	-6.4 (1.15)

122. Secondary Outcome

Title	Change From Baseline to Week 12 in Apolipoprotein B
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	117	114	112	113	119	114	114	119	118	111	116	114
Least Squares Mean (Standard Error) [mg/dL]	5.0 (1.85)	-2.3 (1.87)	-3.6 (1.89)	-0.3 (1.88)	-7.2 (1.83)	-6.1 (1.87)	-2.1 (1.88)	-8.4 (1.83)	-12.2 (1.84)	-6.6 (1.90)	-8.0 (1.86)	-11.7 (1.87)

123. Secondary Outcome

Title	Change From Baseline to Week 26 in Apolipoprotein B
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	118	119	117	125	116	119	122	121	118	120	119
Least Squares Mean (Standard Error) [mg/dL]	0.6 (1.99)	-0.6 (2.00)	-3.7 (2.00)	-1.5 (2.01)	-6.0 (1.95)	-4.8 (2.02)	-3.2 (2.00)	-7.2 (1.97)	-8.8 (1.98)	-3.6 (2.00)	-6.1 (1.99)	-5.5 (2.00)

124. Secondary Outcome

Title	Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis)
Description	Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=337, 352, 345)	-0.6 (0.17)	-1.2 (0.16)	-1.3 (0.17)
Week 26 (n=353, 366, 355)	-0.1 (0.19)	-0.6 (0.19)	-0.6 (0.19)

125. Secondary Outcome

Title	Change From Baseline to Week 12 in Apolipoprotein C-III
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	117	114	112	113	118	114	113	118	118	111	116	113
Least Squares Mean (Standard Error) [mg/dL]	0.7 (0.28)	-0.4 (0.29)	-0.7 (0.29)	-0.3 (0.29)	-1.0 (0.28)	-1.4 (0.29)	-0.3 (0.29)	-1.0 (0.28)	-1.3 (0.28)	-1.1 (0.29)	-1.4 (0.29)	-1.2 (0.29)

126. Secondary Outcome

Title	Change From Baseline to Week 26 in Apolipoprotein C-III
Description	Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	120	118	119	117	125	116	119	121	121	117	120	118
Least Squares Mean (Standard Error) [mg/dL]	0.4 (0.33)	0.5 (0.33)	-0.7 (0.33)	-0.4 (0.33)	-0.6 (0.32)	-0.7 (0.33)	0.2 (0.33)	-0.4 (0.32)	-0.6 (0.32)	0.0 (0.33)	-0.7 (0.33)	-0.5 (0.33)

127. Secondary Outcome

Title	Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis)
Description	Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 345, 343)	-19.6 (3.92)	-28.8 (3.85)	-31.5 (3.86)
Week 26 (n=348, 359, 357)	-11.5 (4.30)	-25.4 (4.23)	-22.9 (4.24)

128. Secondary Outcome

Title	Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides
Description	NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [mg/dL]	20.6 (6.56)	-4.9 (6.73)	-7.8 (6.70)	-12.9 (6.72)	-21.8 (6.70)	-27.2 (6.61)	-18.3 (6.82)	-29.8 (6.73)	-31.6 (6.82)	-27.9 (6.85)	-35.1 (6.59)	-36.0 (6.64)

129. Secondary Outcome

Title	Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides
Description	NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [mg/dL]	12.4 (7.26)	7.3 (7.42)	-6.8 (7.32)	-18.9 (7.44)	-20.4 (7.32)	-23.1 (7.32)	-6.9 (7.44)	-23.5 (7.38)	-19.7 (7.44)	-8.6 (7.44)	-32.1 (7.29)	-25.8 (7.29)

130. Secondary Outcome

Title	Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis)
Description	The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Total Particles - Week 12 (n=332, 345, 343)	-1.85 (1.803)	-6.40 (1.770)	-7.26 (1.775)
Total Particles - Week 26 (n=348, 359, 357)	-1.05 (1.999)	-1.87 (1.970)	-1.31 (1.975)
Large Particles - Week 12 (n=332, 345, 343)	-1.61 (0.289)	-2.20 (0.283)	-2.17 (0.284)
Large Particles - Week 26 (n=348, 359, 357)	-1.05 (0.342)	-2.25 (0.337)	-1.98 (0.337)

131. Secondary Outcome

Title	Change From Baseline to Week 12 in VLDL / Chylomicron Particles
Description	The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Total Particles	5.82 (3.013)	-1.59 (3.092)	-5.32 (3.077)	2.52 (3.089)	-3.46 (3.077)	-5.57 (3.037)	0.45 (3.135)	-7.82 (3.092)	-6.54 (3.132)	-8.58 (3.147)	-7.99 (3.027)	-9.76 (3.051)
Large Particles	1.12 (0.482)	-0.42 (0.495)	-0.27 (0.493)	-1.20 (0.495)	-1.63 (0.493)	-1.81 (0.486)	-1.69 (0.502)	-2.19 (0.495)	-2.29 (0.501)	-1.97 (0.504)	-2.81 (0.484)	-2.45 (0.489)

132. Secondary Outcome

Title	Change From Baseline to Week 26 in VLDL / Chylomicron Particles
Description	The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Total Particles	2.80 (3.379)	0.59 (3.450)	-5.79 (3.405)	-2.99 (3.462)	-3.31 (3.405)	-5.15 (3.405)	3.68 (3.464)	-0.59 (3.436)	-0.35 (3.463)	-3.83 (3.463)	-1.70 (3.394)	1.56 (3.392)
Large Particles	1.31 (0.577)	0.94 (0.589)	-0.14 (0.582)	-1.56 (0.592)	-1.71 (0.582)	-1.80 (0.582)	-0.90 (0.592)	-2.24 (0.587)	-1.79 (0.592)	-0.67 (0.592)	-2.80 (0.580)	-2.36 (0.580)

133. Secondary Outcome

Title	Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis)
Description	The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 345, 343)	-20.4 (3.90)	-28.5 (3.83)	-30.3 (3.84)
Week 26 (n=348, 359, 357)	-13.0 (4.28)	-25.4 (4.22)	-23.0 (4.23)

134. Secondary Outcome

Title	Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides
Description	The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [mg/dL]	19.9 (6.51)	-3.5 (6.69)	-6.4 (6.65)	-14.2 (6.68)	-21.1 (6.65)	-26.5 (6.56)	-19.1 (6.78)	-29.5 (6.69)	-30.1 (6.77)	-28.4 (6.80)	-35.5 (6.55)	-34.8 (6.60)

135. Secondary Outcome

Title	Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides
Description	The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [mg/dL]	11.9 (7.23)	8.3 (7.39)	-7.0 (7.29)	-20.4 (7.41)	-20.4 (7.29)	-23.8 (7.29)	-8.2 (7.41)	-23.5 (7.35)	-18.9 (7.41)	-10.4 (7.41)	-32.3 (7.26)	-26.2 (7.26)

136. Secondary Outcome

Title	Change From Baseline in VLDL Particles Over Time (Grouped Analysis)
Description	The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Medium Particles - Week 12 (n=332, 345, 343)	-4.44 (1.174)	-5.36 (1.152)	-7.30 (1.155)
Medium Particles - Week 26 (n=348, 359, 357)	-2.28 (1.346)	-3.02 (1.326)	-4.88 (1.329)
Small Particles - Week 12 (n=332, 345, 343)	4.16 (1.053)	1.33 (1.033)	1.91 (1.035)
Small Particles - Week 26 (n=348, 359, 357)	2.30 (1.084)	3.55 (1.067)	5.22 (1.070)

137. Secondary Outcome

Title	Change From Baseline to Week 12 in VLDL Particles
Description	The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Medium Particles	2.13 (1.962)	-1.13 (2.014)	-2.88 (2.003)	-2.25 (2.011)	-3.16 (2.004)	-6.51 (1.977)	-2.59 (2.041)	-6.70 (2.013)	-7.05 (2.039)	-8.64 (2.048)	-6.38 (1.971)	-8.50 (1.987)
Small Particles	2.76 (1.758)	0.39 (1.804)	-2.30 (1.797)	5.99 (1.803)	1.16 (1.796)	2.60 (1.772)	4.39 (1.829)	1.15 (1.806)	2.51 (1.828)	2.22 (1.839)	1.80 (1.765)	0.73 (1.780)

138. Secondary Outcome

Title	Change From Baseline to Week 26 in VLDL Particles
Description	The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Medium Particles	1.54 (2.275)	0.85 (2.324)	-2.94 (2.292)	-4.43 (2.331)	-1.78 (2.293)	-5.42 (2.292)	0.28 (2.332)	-2.17 (2.313)	-4.38 (2.331)	-2.70 (2.331)	-5.09 (2.285)	-4.83 (2.284)
Small Particles	0.26 (1.831)	-0.87 (1.868)	-2.91 (1.846)	2.83 (1.876)	-0.19 (1.845)	1.90 (1.845)	4.16 (1.877)	4.07 (1.863)	5.45 (1.876)	-0.08 (1.878)	6.77 (1.837)	8.33 (1.837)

139. Secondary Outcome

Title	Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis)
Description	The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 344, 343)	-2.77 (0.398)	-2.98 (0.390)	-3.02 (0.391)
Week 26 (n=348, 358, 357)	-2.49 (0.406)	-3.67 (0.400)	-3.26 (0.400)

140. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean VLDL Particle Size
Description	The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	113	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [nm]	0.65 (0.664)	0.12 (0.681)	-0.18 (0.678)	-2.81 (0.681)	-2.10 (0.681)	-2.56 (0.669)	-3.16 (0.690)	-2.88 (0.681)	-2.49 (0.690)	-2.37 (0.694)	-4.00 (0.666)	-4.03 (0.672)

141. Secondary Outcome

Title	Change From Baseline to Week 26 in Mean VLDL Particle Size
Description	The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	119	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [nm]	0.26 (0.685)	0.52 (0.700)	0.35 (0.691)	-2.99 (0.703)	-2.66 (0.694)	-2.36 (0.691)	-2.88 (0.703)	-3.69 (0.697)	-3.30 (0.702)	-1.60 (0.703)	-4.65 (0.688)	-4.12 (0.688)

142. Secondary Outcome

Title	Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis)
Description	The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 345, 343)	0.4 (2.16)	-3.9 (2.12)	-5.7 (2.12)
Week 26 (n=348, 359, 357)	2.8 (2.16)	-4.2 (2.13)	-1.5 (2.13)

143. Secondary Outcome

Title	Change From Baseline to Week 12 in IDL Particles
Description	The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [nmol/L]	1.6 (3.60)	-11.1 (3.70)	-6.0 (3.68)	5.1 (3.70)	-6.0 (3.68)	-2.3 (3.64)	-2.2 (3.75)	-6.3 (3.70)	-8.1 (3.75)	-1.5 (3.76)	0.7 (3.62)	-6.5 (3.65)

144. Secondary Outcome

Title	Change From Baseline to Week 26 in IDL Particles
Description	The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [nmol/L]	5.1 (3.65)	-7.3 (3.73)	-3.2 (3.68)	5.2 (3.74)	-2.4 (3.67)	0.0 (3.68)	3.0 (3.74)	-5.0 (3.71)	-5.5 (3.74)	0.1 (3.74)	-5.0 (3.66)	1.0 (3.66)

145. Secondary Outcome

Title	Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis)
Description	The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Total Particles - Week 12 (n=332, 345, 343)	-104.1 (17.46)	-180.5 (17.13)	-236.8 (17.18)
Total Particles - Week 26 (n=348, 359, 357)	-78.2 (17.83)	-146.2 (17.55)	-182.9 (17.60)
Large Particles - Week 12 (n=332, 345, 343)	85.5 (10.02)	111.6 (9.83)	102.3 (9.85)
Large Particles - Week 26 (n=348, 359, 357)	95.8 (11.11)	93.9 (10.93)	106.1 (10.96)
Medium-Small Particles - Week 12 (n=332, 345, 343)	-36.6 (4.11)	-55.3 (4.03)	-60.1 (4.04)
Medium-Small Particles - Week 26 (n=348, 359, 357)	-34.3 (4.22)	-44.9 (4.16)	-49.6 (4.17)
Total Small Particles - Week 12 (n=332, 345, 343)	-191.4 (20.32)	-287.5 (19.94)	-331.4 (20.00)
Total Small Particles - Week 26 (n=348, 359, 357)	-178.1 (21.13)	-235.0 (20.81)	-285.9 (20.87)
Very Small Particles - Week 12 (n=332, 345, 343)	-154.6 (16.53)	-232.3 (16.23)	-271.3 (16.27)
Very Small Particles - Week 26 (n=348, 359, 357)	-143.6 (17.23)	-190.3 (16.97)	-236.2 (17.02)

146. Secondary Outcome

Title	Change From Baseline to Week 12 in LDL Particles
Description	The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Total Particles	52.0 (29.17)	-39.1 (29.92)	-69.9 (29.80)	-48.8 (29.91)	-143.5 (29.79)	-175.6 (29.43)	-96.2 (30.37)	-195.8 (29.93)	-248.8 (30.31)	-167.0 (30.46)	-202.2 (29.27)	-285.8 (29.52)
Large Particles	4.7 (16.74)	21.1 (17.16)	-8.0 (17.09)	56.2 (17.15)	73.8 (17.08)	85.7 (16.86)	83.9 (17.43)	126.2 (17.18)	105.7 (17.39)	116.9 (17.48)	135.2 (16.79)	116.1 (16.95)
Medium-Small Particles	9.4 (6.87)	-7.7 (7.04)	-5.1 (7.02)	-20.3 (7.04)	-41.1 (7.01)	-48.0 (6.93)	-34.4 (7.14)	-58.2 (7.05)	-64.1 (7.14)	-55.4 (7.17)	-66.8 (6.89)	-68.2 (6.96)
Total Small Particles	45.1 (33.98)	-52.0 (34.83)	-56.5 (34.70)	-109.9 (34.83)	-211.0 (34.69)	-256.3 (34.26)	-184.1 (35.32)	-313.7 (34.85)	-345.4 (35.29)	-280.4 (35.46)	-337.9 (34.08)	-392.7 (34.38)
Very Small Particles	36.4 (27.65)	-44.1 (28.34)	-51.9 (28.23)	-89.2 (28.33)	-170.3 (28.22)	-207.6 (27.87)	-149.8 (28.74)	-255.7 (28.36)	-281.5 (28.72)	-225.0 (28.85)	-271.0 (27.73)	-325.0 (27.97)

147. Secondary Outcome

Title	Change From Baseline to Week 26 in LDL Particles
Description	The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Total Particles	15.0 (30.11)	-14.5 (30.73)	-30.8 (30.36)	-46.3 (30.86)	-115.1 (30.35)	-119.4 (30.37)	-68.6 (30.90)	-158.9 (30.62)	-209.4 (30.85)	-119.7 (30.87)	-164.6 (30.22)	-219.9 (30.21)
Large Particles	-23.8 (18.77)	-12.3 (19.14)	15.3 (18.91)	70.5 (19.22)	63.2 (18.90)	93.1 (18.90)	79.3 (19.27)	96.6 (19.09)	102.7 (19.22)	137.7 (19.23)	121.9 (18.83)	122.7 (18.83)
Medium-Small Particles	9.1 (7.14)	0.0 (7.28)	-6.9 (7.20)	-25.8 (7.31)	-29.9 (7.19)	-36.2 (7.20)	-30.0 (7.32)	-47.4 (7.26)	-55.0 (7.31)	-47.1 (7.31)	-57.6 (7.16)	-57.8 (7.17)
Total Small Particles	32.4 (35.72)	2.2 (36.44)	-42.9 (36.00)	-122.5 (36.59)	-175.1 (35.99)	-211.5 (36.01)	-154.9 (36.60)	-248.7 (36.31)	-304.9 (36.58)	-256.9 (36.58)	-281.1 (35.82)	-341.3 (35.82)
Very Small Particles	24.0 (29.13)	2.5 (29.71)	-36.6 (29.36)	-96.3 (29.84)	-145.7 (29.35)	-174.5 (29.37)	-124.9 (29.85)	-201.6 (29.61)	-250.0 (29.83)	-209.6 (29.83)	-223.6 (29.22)	-283.9 (29.21)

148. Secondary Outcome

Title	Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis)
Description	The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 345, 343)	0.43 (0.034)	0.58 (0.034)	0.61 (0.034)
Week 26 (n=348, 359, 357)	0.41 (0.036)	0.47 (0.035)	0.54 (0.036)

149. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean LDL Particle Size
Description	The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [nm]	-0.05 (0.057)	0.13 (0.059)	0.06 (0.059)	0.25 (0.059)	0.43 (0.059)	0.49 (0.058)	0.44 (0.060)	0.61 (0.059)	0.61 (0.060)	0.58 (0.060)	0.68 (0.058)	0.73 (0.058)

150. Secondary Outcome

Title	Change From Baseline to Week 26 in Mean LDL Particle Size
Description	The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [nm]	-0.06 (0.061)	-0.01 (0.062)	0.07 (0.061)	0.26 (0.062)	0.38 (0.061)	0.41 (0.061)	0.38 (0.062)	0.48 (0.062)	0.57 (0.062)	0.59 (0.062)	0.55 (0.061)	0.63 (0.061)

151. Secondary Outcome

Title	Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis)
Description	The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26.

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Total Particles - Week 12 (n=332, 345, 343)	0.86 (0.220)	0.58 (0.216)	0.43 (0.216)
Total Particles - Week 26 (n=348, 359, 357)	0.62 (0.235)	1.18 (0.231)	0.78 (0.232)
Large Particles - Week 12 (n=332, 345, 343)	0.89 (0.111)	0.78 (0.109)	0.89 (0.109)
Large Particles - Week 26 (n=348, 359, 357)	0.81 (0.123)	0.90 (0.121)	1.01 (0.122)
Medium Particles - Week 12 (n=332, 345, 343)	1.38 (0.195)	1.16 (0.191)	1.63 (0.191)
Medium Particles - Week 26 (n=348, 359, 357)	1.34 (0.195)	1.10 (0.192)	1.46 (0.192)
Small Particles - Week 12 (n=332, 345, 343)	-1.35 (0.261)	-1.39 (0.256)	-2.12 (0.256)
Small Particles - Week 26 (n=348, 359, 357)	-1.45 (0.261)	-0.85 (0.257)	-1.73 (0.258)

152. Secondary Outcome

Title	Change From Baseline to Week 12 in HDL Particles
Description	The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Total Particles	-0.08 (0.368)	-0.06 (0.377)	0.16 (0.375)	0.90 (0.377)	0.37 (0.375)	0.55 (0.370)	1.29 (0.382)	0.75 (0.377)	0.15 (0.382)	0.40 (0.384)	0.63 (0.369)	0.60 (0.372)
Large Particles	-0.21 (0.185)	-0.29 (0.190)	-0.10 (0.189)	0.53 (0.190)	0.24 (0.189)	0.50 (0.186)	1.09 (0.192)	0.95 (0.190)	1.12 (0.192)	1.06 (0.193)	1.17 (0.186)	1.06 (0.187)
Medium Particles	0.17 (0.325)	-0.24 (0.333)	-0.01 (0.332)	0.81 (0.334)	1.15 (0.332)	0.65 (0.328)	1.21 (0.338)	0.97 (0.334)	1.89 (0.338)	2.06 (0.339)	1.30 (0.326)	2.31 (0.329)
Small Particles	-0.07 (0.435)	0.43 (0.447)	0.27 (0.445)	-0.25 (0.446)	-1.09 (0.445)	-0.63 (0.439)	-0.92 (0.453)	-1.18 (0.447)	-2.82 (0.452)	-2.82 (0.455)	-1.84 (0.437)	-2.84 (0.441)

153. Secondary Outcome

Title	Change From Baseline to Week 26 in HDL Particles
Description	The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Total Particles	0.18 (0.397)	0.43 (0.405)	1.03 (0.400)	0.37 (0.407)	0.77 (0.400)	1.31 (0.400)	0.67 (0.407)	1.15 (0.403)	0.26 (0.406)	0.83 (0.407)	1.61 (0.398)	0.77 (0.398)
Large Particles	0.02 (0.208)	-0.16 (0.212)	0.39 (0.210)	0.53 (0.213)	0.55 (0.210)	0.75 (0.210)	0.64 (0.213)	1.13 (0.212)	1.34 (0.213)	1.26 (0.213)	1.02 (0.209)	0.95 (0.209)
Medium Particles	0.13 (0.330)	0.16 (0.336)	0.54 (0.332)	0.81 (0.338)	0.86 (0.332)	0.67 (0.332)	1.48 (0.338)	1.47 (0.335)	1.69 (0.337)	1.71 (0.337)	0.96 (0.331)	2.01 (0.330)
Small Particles	0.00 (0.441)	0.41 (0.450)	0.10 (0.444)	-0.78 (0.452)	-0.68 (0.444)	-0.17 (0.444)	-1.35 (0.452)	-1.47 (0.448)	-2.77 (0.452)	-2.21 (0.452)	-0.40 (0.443)	-2.24 (0.442)

154. Secondary Outcome

Title	Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis)
Description	The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time Frame	Baseline and Weeks 12 and 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Pioglitazone Alone	Alogliptin 12.5 + Pioglitazone	Alogliptin 25 + Pioglitazone
Arm/Group Description	Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Measure Participants	387	390	390
Week 12 (n=332, 345, 343)	0.11 (0.013)	0.13 (0.013)	0.16 (0.013)
Week 26 (n=348, 359, 357)	0.11 (0.015)	0.12 (0.014)	0.17 (0.014)

155. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean HDL Particle Size
Description	The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	119	113	114	113	114	117	110	113	110	109	118	116
Least Squares Mean (Standard Error) [nm]	0.00 (0.023)	0.00 (0.023)	0.00 (0.023)	0.06 (0.023)	0.07 (0.023)	0.09 (0.023)	0.10 (0.023)	0.15 (0.023)	0.17 (0.023)	0.18 (0.024)	0.17 (0.023)	0.21 (0.023)

156. Secondary Outcome

Title	Change From Baseline to Week 26 in Mean HDL Particle Size
Description	The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Arm/Group Title	Placebo	Alogliptin 12.5 + Placebo	Alogliptin 25 + Placebo	Placebo + Pioglitazone 15	Alogliptin 12.5 + Pioglitazone 15	Alogliptin 25 + Pioglitazone 15	Placebo + Pioglitazone 30	Alogliptin 12.5 + Pioglitazone 30	Alogliptin 25 + Pioglitazone 30	Placebo + Pioglitazone 45	Alogliptin 12.5 + Pioglitazone 45	Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Measure Participants	122	117	120	116	120	120	116	118	116	116	121	121
Least Squares Mean (Standard Error) [nm]	0.03 (0.025)	0.00 (0.025)	0.07 (0.025)	0.06 (0.025)	0.06 (0.025)	0.11 (0.025)	0.10 (0.025)	0.15 (0.025)	0.20 (0.025)	0.19 (0.025)	0.16 (0.025)	0.19 (0.025)

Adverse Events

	Placebo		Alogliptin 12.5 + Placebo		Alogliptin 25 + Placebo		Placebo + Pioglitazone 15		Alogliptin 12.5 + Pioglitazone 15		Alogliptin 25 + Pioglitazone 15		Placebo + Pioglitazone 30		Alogliptin 12.5 + Pioglitazone 30		Alogliptin 25 + Pioglitazone 30		Placebo + Pioglitazone 45		Alogliptin 12.5 + Pioglitazone 45		Alogliptin 25 + Pioglitazone 45
Time Frame	Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment.
Adverse Event Reporting Description	At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.

Arm/Group Title	Placebo		Alogliptin 12.5 + Placebo		Alogliptin 25 + Placebo		Placebo + Pioglitazone 15		Alogliptin 12.5 + Pioglitazone 15		Alogliptin 25 + Pioglitazone 15		Placebo + Pioglitazone 30		Alogliptin 12.5 + Pioglitazone 30		Alogliptin 25 + Pioglitazone 30		Placebo + Pioglitazone 45		Alogliptin 12.5 + Pioglitazone 45		Alogliptin 25 + Pioglitazone 45
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.		Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.		Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.		Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.		Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Alogliptin 12.5 + Placebo		Alogliptin 25 + Placebo		Placebo + Pioglitazone 15		Alogliptin 12.5 + Pioglitazone 15		Alogliptin 25 + Pioglitazone 15		Placebo + Pioglitazone 30		Alogliptin 12.5 + Pioglitazone 30		Alogliptin 25 + Pioglitazone 30		Placebo + Pioglitazone 45		Alogliptin 12.5 + Pioglitazone 45		Alogliptin 25 + Pioglitazone 45
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/129 (1.6%)		5/128 (3.9%)		6/129 (4.7%)		1/129 (0.8%)		2/130 (1.5%)		1/130 (0.8%)		2/129 (1.6%)		3/130 (2.3%)		6/130 (4.6%)		10/129 (7.8%)		2/130 (1.5%)		5/130 (3.8%)
Cardiac disorders
Angina unstable	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)
Coronary artery disease	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Coronary artery stenosis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)
Myocardial infarction	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Myocardial ischaemia	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)
Gastrointestinal disorders
Gastritis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Pancreatitis	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Periodontitis	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Reflux oesophagitis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Umbilical hernia	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
General disorders
Non-cardiac chest pain	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Pyrexia	1/129 (0.8%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Sudden cardiac death	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Hepatobiliary disorders
Cholangitis	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Cholecystitis	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Cholecystitis acute	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Cholelithiasis	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Hepatitis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Infections and infestations
Appendicitis	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)
Pneumonia	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Arthritis bacterial	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Bronchopneumonia	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Gastroenteritis viral	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Lower respiratory tract infection	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Osteomyelitis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Perirectal abscess	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Pyelonephritis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Pyelonephritis acute	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Urinary tract infection	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)
Foreign body in eye	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Nervous system disorders
Carotid artery occlusion	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Cerebrovascular accident	1/129 (0.8%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Convulsion	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Disturbance in attention	0/129 (0%)		0/128 (0%)		0/129 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Ischaemic stroke	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Lacunar infarction	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)
Migraine with aura	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Nerve compression	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Syncope	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/129 (0%)		1/128 (0.8%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Psychiatric disorders
Anxiety	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		1/129 (0.8%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Renal and urinary disorders
Calculus ureteric	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)
Nephrolithiasis	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Respiratory, thoracic and mediastinal disorders
Lung cyst benign	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		1/130 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Pulmonary congestion	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)
Pulmonary embolism	0/129 (0%)		0/128 (0%)		1/129 (0.8%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Vascular disorders
Peripheral vascular disorder	0/129 (0%)		0/128 (0%)		0/129 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)		0/129 (0%)		1/130 (0.8%)		0/130 (0%)		0/129 (0%)		0/130 (0%)		0/130 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Alogliptin 12.5 + Placebo		Alogliptin 25 + Placebo		Placebo + Pioglitazone 15		Alogliptin 12.5 + Pioglitazone 15		Alogliptin 25 + Pioglitazone 15		Placebo + Pioglitazone 30		Alogliptin 12.5 + Pioglitazone 30		Alogliptin 25 + Pioglitazone 30		Placebo + Pioglitazone 45		Alogliptin 12.5 + Pioglitazone 45		Alogliptin 25 + Pioglitazone 45
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/129 (31.8%)		40/128 (31.3%)		46/129 (35.7%)		51/129 (39.5%)		45/130 (34.6%)		44/130 (33.8%)		40/129 (31%)		35/130 (26.9%)		51/130 (39.2%)		40/129 (31%)		47/130 (36.2%)		41/130 (31.5%)
Blood and lymphatic system disorders
Anaemia	2/129 (1.6%)		0/128 (0%)		0/129 (0%)		2/129 (1.6%)		2/130 (1.5%)		2/130 (1.5%)		3/129 (2.3%)		3/130 (2.3%)		7/130 (5.4%)		0/129 (0%)		3/130 (2.3%)		5/130 (3.8%)
Gastrointestinal disorders
Diarrhoea	11/129 (8.5%)		2/128 (1.6%)		4/129 (3.1%)		5/129 (3.9%)		3/130 (2.3%)		6/130 (4.6%)		4/129 (3.1%)		2/130 (1.5%)		7/130 (5.4%)		5/129 (3.9%)		4/130 (3.1%)		7/130 (5.4%)
Abdominal pain upper	2/129 (1.6%)		0/128 (0%)		7/129 (5.4%)		0/129 (0%)		1/130 (0.8%)		2/130 (1.5%)		1/129 (0.8%)		1/130 (0.8%)		3/130 (2.3%)		1/129 (0.8%)		5/130 (3.8%)		0/130 (0%)
General disorders
Oedema peripheral	2/129 (1.6%)		2/128 (1.6%)		2/129 (1.6%)		2/129 (1.6%)		2/130 (1.5%)		7/130 (5.4%)		6/129 (4.7%)		4/130 (3.1%)		1/130 (0.8%)		2/129 (1.6%)		4/130 (3.1%)		6/130 (4.6%)
Infections and infestations
Urinary tract infection	6/129 (4.7%)		6/128 (4.7%)		5/129 (3.9%)		7/129 (5.4%)		5/130 (3.8%)		6/130 (4.6%)		8/129 (6.2%)		4/130 (3.1%)		4/130 (3.1%)		8/129 (6.2%)		5/130 (3.8%)		5/130 (3.8%)
Nasopharyngitis	5/129 (3.9%)		5/128 (3.9%)		4/129 (3.1%)		3/129 (2.3%)		8/130 (6.2%)		8/130 (6.2%)		4/129 (3.1%)		5/130 (3.8%)		9/130 (6.9%)		4/129 (3.1%)		6/130 (4.6%)		4/130 (3.1%)
Influenza	3/129 (2.3%)		4/128 (3.1%)		4/129 (3.1%)		9/129 (7%)		4/130 (3.1%)		8/130 (6.2%)		7/129 (5.4%)		2/130 (1.5%)		8/130 (6.2%)		5/129 (3.9%)		3/130 (2.3%)		2/130 (1.5%)
Upper respiratory tract infection	5/129 (3.9%)		3/128 (2.3%)		8/129 (6.2%)		3/129 (2.3%)		2/130 (1.5%)		4/130 (3.1%)		1/129 (0.8%)		5/130 (3.8%)		4/130 (3.1%)		2/129 (1.6%)		4/130 (3.1%)		4/130 (3.1%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	3/129 (2.3%)		7/128 (5.5%)		6/129 (4.7%)		5/129 (3.9%)		2/130 (1.5%)		3/130 (2.3%)		5/129 (3.9%)		2/130 (1.5%)		4/130 (3.1%)		3/129 (2.3%)		3/130 (2.3%)		1/130 (0.8%)
Dyslipidaemia	0/129 (0%)		1/128 (0.8%)		1/129 (0.8%)		3/129 (2.3%)		3/130 (2.3%)		1/130 (0.8%)		2/129 (1.6%)		1/130 (0.8%)		4/130 (3.1%)		7/129 (5.4%)		1/130 (0.8%)		2/130 (1.5%)
Musculoskeletal and connective tissue disorders
Back pain	5/129 (3.9%)		1/128 (0.8%)		7/129 (5.4%)		5/129 (3.9%)		6/130 (4.6%)		5/130 (3.8%)		3/129 (2.3%)		2/130 (1.5%)		8/130 (6.2%)		4/129 (3.1%)		12/130 (9.2%)		3/130 (2.3%)
Nervous system disorders
Headache	6/129 (4.7%)		5/128 (3.9%)		9/129 (7%)		16/129 (12.4%)		5/130 (3.8%)		3/130 (2.3%)		2/129 (1.6%)		2/130 (1.5%)		5/130 (3.8%)		5/129 (3.9%)		6/130 (4.6%)		6/130 (4.6%)
Dizziness	4/129 (3.1%)		3/128 (2.3%)		2/129 (1.6%)		5/129 (3.9%)		7/130 (5.4%)		2/130 (1.5%)		4/129 (3.1%)		5/130 (3.8%)		5/130 (3.8%)		6/129 (4.7%)		6/130 (4.6%)		1/130 (0.8%)
Vascular disorders
Hypertension	4/129 (3.1%)		6/128 (4.7%)		4/129 (3.1%)		6/129 (4.7%)		9/130 (6.9%)		3/130 (2.3%)		2/129 (1.6%)		3/130 (2.3%)		3/130 (2.3%)		2/129 (1.6%)		5/130 (3.8%)		1/130 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

Results Point of Contact

Name/Title	Sr. VP, Clinical Science
Organization	Takeda Global Research and Development Center, Inc.
Phone	800-778-2860
Email	clinicaltrialregistry@tpna.com

Responsible Party:

Takeda

ClinicalTrials.gov Identifier:

NCT00328627

Other Study ID Numbers:

01-05-TL-322OPI-001
2006-000694-30
U1111-1113-8587

First Posted:

May 22, 2006

Last Update Posted:

Apr 4, 2013

Last Verified:

Feb 1, 2013