Trial Outcomes & Findings for Study of Alogliptin Combined With Pioglitazone in Subjects With Type 2 Diabetes Mellitus (NCT NCT00286494)

Results Overview

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

493 participants

Primary outcome timeframe

Baseline and Week 26.

Results posted on

2012-02-03

Participant Flow

Participants enrolled at 125 investigative sites in 13 countries from 24 February 2006 to 02 August 2007.

Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled in one of 3, once-daily (QD) treatment groups.

Participant milestones

Participant milestones
Measure	Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study STARTED	97	197	199
Overall Study COMPLETED	71	153	160
Overall Study NOT COMPLETED	26	44	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study Hyperglycemic rescue	12	19	18
Overall Study Withdrawal by Subject	2	10	9
Overall Study Adverse Event	3	8	6
Overall Study Physician Decision	5	5	1
Overall Study Lost to Follow-up	3	1	3
Overall Study Protocol Violation	1	1	2

Baseline Characteristics

Study of Alogliptin Combined With Pioglitazone in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Total n=493 Participants Total of all reporting groups
Age, Customized <65 years	83 participants n=5 Participants	165 participants n=7 Participants	160 participants n=5 Participants	408 participants n=4 Participants
Age, Customized Between 65 and 74 years	10 participants n=5 Participants	29 participants n=7 Participants	34 participants n=5 Participants	73 participants n=4 Participants
Age, Customized ≥75 years	4 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	12 participants n=4 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	88 Participants n=7 Participants	74 Participants n=5 Participants	206 Participants n=4 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	109 Participants n=7 Participants	125 Participants n=5 Participants	287 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=195 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.	-0.19 percentage of Glycosylated Hemoglobin Standard Error 0.081	-0.66 percentage of Glycosylated Hemoglobin Standard Error 0.056	-0.80 percentage of Glycosylated Hemoglobin Standard Error 0.056

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=182 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=176 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 4).	-0.14 percentage of Glycosylated Hemoglobin Standard Error 0.042	-0.40 percentage of Glycosylated Hemoglobin Standard Error 0.029	-0.45 percentage of Glycosylated Hemoglobin Standard Error 0.030

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=195 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 8).	-0.18 percentage of Glycosylated Hemoglobin Standard Error 0.061	-0.60 percentage of Glycosylated Hemoglobin Standard Error 0.042	-0.73 percentage of Glycosylated Hemoglobin Standard Error 0.042

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=195 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 12).	-0.23 percentage of Glycosylated Hemoglobin Standard Error 0.069	-0.70 percentage of Glycosylated Hemoglobin Standard Error 0.048	-0.82 percentage of Glycosylated Hemoglobin Standard Error 0.048

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=195 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 16).	-0.26 percentage of Glycosylated Hemoglobin Standard Error 0.076	-0.70 percentage of Glycosylated Hemoglobin Standard Error 0.053	-0.84 percentage of Glycosylated Hemoglobin Standard Error 0.053

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=195 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 20).	-0.27 percentage of Glycosylated Hemoglobin Standard Error 0.078	-0.68 percentage of Glycosylated Hemoglobin Standard Error 0.055	-0.82 percentage of Glycosylated Hemoglobin Standard Error 0.055

SECONDARY outcome

Timeframe: Baseline and Week 1.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=176 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=171 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 1).	-2.7 mg/dL Standard Error 3.11	-14.2 mg/dL Standard Error 2.20	-18.2 mg/dL Standard Error 2.22

SECONDARY outcome

Timeframe: Baseline and Week 2.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=189 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=193 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 2).	-1.8 mg/dL Standard Error 2.97	-21.0 mg/dL Standard Error 2.13	-21.2 mg/dL Standard Error 2.10

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).Smaller "n" at earlier timepoints due to unavailable prior values to carry forward

The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=194 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 4).	-3.1 mg/dL Standard Error 2.88	-23.7 mg/dL Standard Error 2.04	-26.0 mg/dL Standard Error 2.02

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 8).	-6.1 mg/dL Standard Error 3.26	-22.6 mg/dL Standard Error 2.30	-27.1 mg/dL Standard Error 2.29

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 12).	-9.9 mg/dL Standard Error 3.33	-20.4 mg/dL Standard Error 2.34	-26.2 mg/dL Standard Error 2.33

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 16).	-8.3 mg/dL Standard Error 3.71	-18.3 mg/dL Standard Error 2.61	-22.8 mg/dL Standard Error 2.60

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 20).	-6.4 mg/dL Standard Error 3.58	-21.9 mg/dL Standard Error 2.52	-21.6 mg/dL Standard Error 2.51

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=197 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 26).	-5.7 mg/dL Standard Error 3.81	-19.7 mg/dL Standard Error 2.68	-19.9 mg/dL Standard Error 2.67

SECONDARY outcome

Timeframe: 26 Weeks.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set) and had at least 1 post-baseline FPG measurement.

The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=198 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).	43 participants	49 participants	43 participants

SECONDARY outcome

Timeframe: 26 Weeks.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set)and at least 1 post-baseline measurement.

The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=196 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants Requiring Rescue.	12 participants	19 participants	18 participants

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of fasting proinsulin collected at week 4 and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=172 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=169 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 4).	-0.7 pmol/L Standard Error 1.74	-7.0 pmol/L Standard Error 1.24	-5.6 pmol/L Standard Error 1.25

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of fasting proinsulin collected at week 8 and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 8).	-2.3 pmol/L Standard Error 1.70	-6.5 pmol/L Standard Error 1.19	-3.7 pmol/L Standard Error 1.19

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting proinsulin collected at week 12 and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 12).	0.6 pmol/L Standard Error 1.88	-3.6 pmol/L Standard Error 1.33	-3.8 pmol/L Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting proinsulin collected at week 16 and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 16).	-3.1 pmol/L Standard Error 1.89	-3.5 pmol/L Standard Error 1.33	-3.1 pmol/L Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting proinsulin collected at week 20 and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 20).	-0.9 pmol/L Standard Error 1.67	-6.2 pmol/L Standard Error 1.18	-3.9 pmol/L Standard Error 1.17

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of fasting proinsulin collected at week 26 or final visit and fasting proinsulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 26).	-1.0 pmol/L Standard Error 1.9	-5.1 pmol/L Standard Error 1.34	-1.7 pmol/L Standard Error 1.33

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of insulin collected at week 4 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=166 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=165 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 4).	-0.09 mcIU/mL Standard Error 0.694	-1.08 mcIU/mL Standard Error 0.501	-0.97 mcIU/mL Standard Error 0.501

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of insulin collected at week 8 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 8).	-0.17 mcIU/mL Standard Error 0.748	-0.82 mcIU/mL Standard Error 0.531	0.21 mcIU/mL Standard Error 0.522

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of insulin collected at week 12 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 12).	0.00 mcIU/mL Standard Error 1.085	0.43 mcIU/mL Standard Error 0.771	-0.58 mcIU/mL Standard Error 0.757

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of insulin collected at week 16 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 16).	-0.85 mcIU/mL Standard Error 0.701	-0.10 mcIU/mL Standard Error 0.501	-0.16 mcIU/mL Standard Error 0.492

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of insulin collected at week 20 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 20).	-0.19 mcIU/mL Standard Error 0.690	-0.40 mcIU/mL Standard Error 0.490	-0.33 mcIU/mL Standard Error 0.481

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of insulin collected at week 26 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 26).	-0.81 mcIU/mL Standard Error 0.711	-0.19 mcIU/mL Standard Error 0.505	0.00 mcIU/mL Standard Error 0.495

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the ratio value of proinsulin and insulin collected at week 4 and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=166 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=165 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 4).	0.006 ratio Standard Error 0.0144	-0.051 ratio Standard Error 0.0104	-0.053 ratio Standard Error 0.0104

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the ratio value of proinsulin and insulin collected at week 8 and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 8).	-0.006 ratio Standard Error 0.0145	-0.055 ratio Standard Error 0.0103	-0.057 ratio Standard Error 0.0101

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the ratio value of proinsulin and insulin collected at week 12 and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 12).	0.017 ratio Standard Error 0.0190	-0.029 ratio Standard Error 0.0135	-0.040 ratio Standard Error 0.0132

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the ratio value of proinsulin and insulin collected at week 16 and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 16).	-0.015 ratio Standard Error 0.0153	-0.042 ratio Standard Error 0.0109	-0.045 ratio Standard Error 0.0107

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the ratio value of proinsulin and insulin collected at week 20 and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 20).	0.012 ratio Standard Error 0.0168	-0.047 ratio Standard Error 0.0119	-0.040 ratio Standard Error 0.0117

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the ratio value of proinsulin and insulin collected at week 26 or final visit and the ratio value of proinsulin and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 26).	0.015 ratio Standard Error 0.0185	-0.035 ratio Standard Error 0.0131	-0.022 ratio Standard Error 0.0129

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=181 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=175 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 4).	-0.144 ng/mL Standard Error 0.1108	-0.156 ng/mL Standard Error 0.0783	-0.088 ng/mL Standard Error 0.0794

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=195 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=194 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 8).	-0.111 ng/mL Standard Error 0.1127	-0.117 ng/mL Standard Error 0.0787	0.023 ng/mL Standard Error 0.0788

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=195 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=194 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 12).	-0.017 ng/mL Standard Error 0.1226	-0.085 ng/mL Standard Error 0.0856	-0.067 ng/mL Standard Error 0.0856

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=195 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=194 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 16).	-0.290 ng/mL Standard Error 0.1135	-0.071 ng/mL Standard Error 0.0793	-0.052 ng/mL Standard Error 0.0793

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=195 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=194 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 20).	-0.255 ng/mL Standard Error 0.1029	-0.228 ng/mL Standard Error 0.0718	-0.123 ng/mL Standard Error 0.0719

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=195 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=194 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 26).	-0.356 ng/mL Standard Error 0.1071	-0.233 ng/mL Standard Error 0.0748	-0.133 ng/mL Standard Error 0.0748

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.	5 participants	34 participants	41 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a value for the percentage of glycosylated hemoglobin less (the percentage of hemoglobin that is bound to glucose) than or equal to 7.0% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.	33 participants	87 participants	98 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.	47 participants	127 participants	141 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.	26 participants	118 participants	128 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.	12 participants	64 participants	73 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.	5 participants	32 participants	37 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set).

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=197 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.	3 participants	12 participants	14 participants

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF). Smaller "n" at earlier timepoints due to unavailable prior values to carry forward.

The change between Body Weight measured at week 8 and Body Weight measured at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=190 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=186 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 8).	0.36 kg Standard Error 0.228	0.46 kg Standard Error 0.160	0.39 kg Standard Error 0.161

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between Body Weight measured at week 12 and Body Weight measured at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=193 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=189 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 12).	0.60 kg Standard Error 0.267	0.74 kg Standard Error 0.187	0.64 kg Standard Error 0.188

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between Body Weight measured at week 20 and Body Weight measured at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=193 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=189 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 20).	0.94 kg Standard Error 0.318	1.14 kg Standard Error 0.222	0.93 kg Standard Error 0.224

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=193 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=189 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg or 45 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 26).	1.04 kg Standard Error 0.329	1.46 kg Standard Error 0.230	1.09 kg Standard Error 0.232

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 38 other events

Deaths: 0 deaths

Alogliptin 12.5 mg QD

Serious events: 5 serious events

Other events: 76 other events

Deaths: 0 deaths

Alogliptin 25 mg QD

Serious events: 13 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER