Trial Outcomes & Findings for Efficacy and Safety of Alogliptin Combined With Metformin in Participants With Type 2 Diabetes Mellitus (NCT NCT00286442)

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

527 participants

Primary outcome timeframe

Baseline and Week 26.

Results posted on

2012-02-03

Participant Flow

Participants enrolled at 115 investigative sites in Australia, Brazil, Chile, Germany, Guatemala, Hungary, India, Mexico, New Zealand, The Netherlands, Poland, South Africa, Spain, and the United States from 10 March 2006 to 12 June 2007.

Participants with a historical diagnosis of type 2 diabetes mellitus who were inadequately controlled while receiving a stable dose of metformin monotherapy were enrolled in one of 3, once-daily (QD) treatment groups.

Participant milestones

Participant milestones
Measure	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Study STARTED	213	210	104
Overall Study COMPLETED	176	165	72
Overall Study NOT COMPLETED	37	45	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Study Hyperglycemic Rescue	19	17	25
Overall Study Adverse Event	7	6	1
Overall Study Protocol Violation	2	4	2
Overall Study Lost to Follow-up	5	2	1
Overall Study Physician Decision	1	1	1
Overall Study Administrative Error	1	1	0
Overall Study Withdrawal by Subject	2	14	2

Baseline Characteristics

Efficacy and Safety of Alogliptin Combined With Metformin in Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=210 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.	Total n=527 Participants Total of all reporting groups
Age, Customized <65 years	173 participants n=5 Participants	179 participants n=7 Participants	83 participants n=5 Participants	435 participants n=4 Participants
Age, Customized ≥65 years	40 participants n=5 Participants	31 participants n=7 Participants	21 participants n=5 Participants	92 participants n=4 Participants
Sex: Female, Male Female	112 Participants n=5 Participants	96 Participants n=7 Participants	54 Participants n=5 Participants	262 Participants n=4 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	114 Participants n=7 Participants	50 Participants n=5 Participants	265 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 26.

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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=203 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.	-0.61 percentage of Glycosylated Hemoglobin Standard Error 0.053	-0.59 percentage of Glycosylated Hemoglobin Standard Error 0.054	-0.10 percentage of Glycosylated Hemoglobin Standard Error 0.076

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 4. 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 4 and Glycosylated Hemoglobin collected at baseline.

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=188 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=187 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=91 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 4).	-0.36 percentage of Glycosylated Hemoglobin Standard Error 0.031	-0.40 percentage of Glycosylated Hemoglobin Standard Error 0.031	-0.10 percentage of Glycosylated Hemoglobin Standard Error 0.044

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 8.

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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=201 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 8).	-0.59 percentage of Glycosylated Hemoglobin Standard Error 0.041	-0.59 percentage of Glycosylated Hemoglobin Standard Error 0.042	-0.21 percentage of Glycosylated Hemoglobin Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 12.

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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=203 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 12).	-0.66 percentage of Glycosylated Hemoglobin Standard Error 0.047	-0.66 percentage of Glycosylated Hemoglobin Standard Error 0.048	-0.16 percentage of Glycosylated Hemoglobin Standard Error 0.067

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 16.

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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=203 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 16).	-0.66 percentage of Glycosylated Hemoglobin Standard Error 0.050	-0.64 percentage of Glycosylated Hemoglobin Standard Error 0.051	-0.13 percentage of Glycosylated Hemoglobin Standard Error 0.072

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 20.

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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=203 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 20).	-0.63 percentage of Glycosylated Hemoglobin Standard Error 0.051	-0.63 percentage of Glycosylated Hemoglobin Standard Error 0.052	-0.12 percentage of Glycosylated Hemoglobin Standard Error 0.073

SECONDARY outcome

Timeframe: Baseline and Week 1.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 1.

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	Alogliptin 12.5 mg QD n=193 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=186 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=98 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 1).	-14.3 mg/dL Standard Error 2.05	-12.5 mg/dL Standard Error 2.09	-0.6 mg/dL Standard Error 2.88

SECONDARY outcome

Timeframe: Baseline and Week 2.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 2.

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	Alogliptin 12.5 mg QD n=208 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=199 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 2).	-17.4 mg/dL Standard Error 2.11	-17.6 mg/dL Standard Error 2.16	-0.7 mg/dL Standard Error 2.99

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 2. Missing data imputed using last observation carried forward (LOCF).

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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 4).	-18.4 mg/dL Standard Error 1.98	-18.1 mg/dL Standard Error 2.01	-0.6 mg/dL Standard Error 2.82

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 8. 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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 8).	-19.6 mg/dL Standard Error 2.30	-17.2 mg/dL Standard Error 2.34	0.4 mg/dL Standard Error 3.29

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 12).	-16.9 mg/dL Standard Error 2.44	-16.8 mg/dL Standard Error 2.47	0.3 mg/dL Standard Error 3.48

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 16. 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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 16).	-17.8 mg/dL Standard Error 2.43	-15.4 mg/dL Standard Error 2.46	1.3 mg/dL Standard Error 3.46

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 20).	-18.1 mg/dL Standard Error 2.53	-15.6 mg/dL Standard Error 2.57	-0.1 mg/dL Standard Error 3.61

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 26. 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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=204 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 26).	-18.7 mg/dL Standard Error 2.49	-17.4 mg/dL Standard Error 2.53	0.0 mg/dL Standard Error 3.55

SECONDARY outcome

Timeframe: 26 Weeks.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 fasting plasma glucose measurement after baseline.

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	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=206 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).	61 participants	65 participants	53 participants

SECONDARY outcome

Timeframe: 26 Weeks.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 study visit after baseline.

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=211 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants Requiring Rescue.	19 participants	17 participants	25 participants

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=178 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=174 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=90 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 4).	-1.9 pmol/L Standard Error 1.76	-5.0 pmol/L Standard Error 1.77	-0.5 pmol/L Standard Error 2.47

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=201 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=189 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=100 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 8).	-2.9 pmol/L Standard Error 1.30	-5.0 pmol/L Standard Error 1.34	-0.4 pmol/L Standard Error 1.85

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=201 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=191 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=100 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 12).	-2.6 pmol/L Standard Error 1.76	-2.7 pmol/L Standard Error 1.8	-1.3 pmol/L Standard Error 2.49

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 16. 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	Alogliptin 12.5 mg QD n=201 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=191 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=100 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 16).	-1.4 pmol/L Standard Error 1.60	-2.7 pmol/L Standard Error 1.64	-0.5 pmol/L Standard Error 2.26

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=201 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=191 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=100 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 20).	-4.2 pmol/L Standard Error 1.62	-1.1 pmol/L Standard Error 1.66	-2.0 pmol/L Standard Error 2.29

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a PROINSULIN measurement at baseline and at Week 26. 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	Alogliptin 12.5 mg QD n=201 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=191 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=100 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 26).	-2.1 pmol/L Standard Error 1.80	-1.6 pmol/L Standard Error 1.84	-3.2 pmol/L Standard Error 2.54

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an insulin measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=177 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=170 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=89 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 4).	1.11 mcIU/mL Standard Error 0.684	0.52 mcIU/mL Standard Error 0.695	-1.07 mcIU/mL Standard Error 0.965

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 8. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=186 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 8).	2.50 mcIU/mL Standard Error 1.416	0.18 mcIU/mL Standard Error 1.466	2.68 mcIU/mL Standard Error 2.015

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 12).	1.6 mcIU/mL Standard Error 1.488	0.46 mcIU/mL Standard Error 1.532	1.92 mcIU/mL Standard Error 2.118

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 16. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 16).	1.27 mcIU/mL Standard Error 0.964	1.53 mcIU/mL Standard Error 0.993	0.64 mcIU/mL Standard Error 1.372

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 20).	0.91 mcIU/mL Standard Error 0.760	0.86 mcIU/mL Standard Error 0.782	-0.21 mcIU/mL Standard Error 1.081

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Insulin (Week 26).	0.63 mcIU/mL Standard Error 0.690	-0.01 mcIU/mL Standard Error 0.710	-2.23 mcIU/mL Standard Error 0.981

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

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	Alogliptin 12.5 mg QD n=177 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=170 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=89 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 4).	-0.045 ratio Standard Error 0.0082	-0.056 ratio Standard Error 0.0083	-0.008 ratio Standard Error 0.0115

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 8. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=186 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 8).	-0.055 ratio Standard Error 0.0073	-0.046 ratio Standard Error 0.0075	-0.009 ratio Standard Error 0.0103

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 12).	-0.044 ratio Standard Error 0.0083	-0.042 ratio Standard Error 0.0085	-0.005 ratio Standard Error 0.0118

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 16. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 16).	-0.051 ratio Standard Error 0.0082	-0.043 ratio Standard Error 0.0085	0.001 ratio Standard Error 0.0117

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 20).	-0.53 ratio Standard Error 0.0150	-0.011 ratio Standard Error 0.0155	-0.007 ratio Standard Error 0.0213

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 26. 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	Alogliptin 12.5 mg QD n=200 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=188 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=99 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 26).	-0.049 ratio Standard Error 0.0154	0.000 ratio Standard Error 0.0159	0.004 ratio Standard Error 0.0219

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=186 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=184 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=92 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 4).	0.222 ng/mL Standard Error 0.0893	0.190 ng/mL Standard Error 0.0897	-0.114 ng/mL Standard Error 0.1273

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 8. 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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=200 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 8).	0.215 ng/mL Standard Error 0.0864	0.238 ng/mL Standard Error 0.0884	0.127 ng/mL Standard Error 0.1236

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=202 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 12).	0.154 ng/mL Standard Error 0.0915	0.246 ng/mL Standard Error 0.0932	-0.033 ng/mL Standard Error 0.1309

SECONDARY outcome

Timeframe: Baseline and Week 16.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 16. 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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=202 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 16).	0.138 ng/mL Standard Error 0.0894	0.250 ng/mL Standard Error 0.0910	-0.018 ng/mL Standard Error 0.1280

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=202 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 20).	0.007 ng/mL Standard Error 0.0803	0.054 ng/mL Standard Error 0.0818	-0.137 ng/mL Standard Error 0.1149

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 26. 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	Alogliptin 12.5 mg QD n=210 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=202 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in C-peptide (Week 26).	-0.083 ng/mL Standard Error 0.0833	-0.214 ng/mL Standard Error 0.0848	-0.476 ng/mL Standard Error 0.1192

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.	42 participants	36 participants	4 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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 7.0% during the 26 week study.

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.	110 participants	92 participants	19 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.	153 participants	137 participants	47 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.	123 participants	122 participants	28 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.	61 participants	62 participants	9 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.	20 participants	24 participants	6 participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 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	Alogliptin 12.5 mg QD n=213 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.	7 participants	5 participants	4 participants

SECONDARY outcome

Timeframe: Baseline and Week 8.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had weight measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

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

Outcome measures

Outcome measures
Measure	Alogliptin 12.5 mg QD n=198 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=193 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=102 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Body Weight (Week 8).	-0.30 kg Standard Error 0.134	-0.53 kg Standard Error 0.135	-0.12 kg Standard Error 0.186

SECONDARY outcome

Timeframe: Baseline and Week 12.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had weight measurements at baseline and at Week 12. 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	Alogliptin 12.5 mg QD n=205 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=198 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Body Weight (Week 12).	-0.28 kg Standard Error 0.161	-0.64 kg Standard Error 0.164	-0.57 kg Standard Error 0.227

SECONDARY outcome

Timeframe: Baseline and Week 20.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had weight measurements at baseline and at Week 20. 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	Alogliptin 12.5 mg QD n=205 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=198 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Body Weight (Week 20).	-0.38 kg Standard Error 0.178	-0.58 kg Standard Error 0.182	-0.40 kg Standard Error 0.252

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had weight measurements at baseline and at Week 26. 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	Alogliptin 12.5 mg QD n=206 Participants Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=198 Participants Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=103 Participants Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Change From Baseline in Body Weight (Week 26).	-0.39 kg Standard Error 0.194	-0.67 kg Standard Error 0.198	-0.39 kg Standard Error 0.274

Adverse Events

Alogliptin 12.5 mg QD

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

Alogliptin 25 mg QD

Serious events: 8 serious events

Other events: 41 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Alogliptin 12.5 mg QD n=213 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Alogliptin 25 mg QD n=207 participants at risk Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.	Placebo n=104 participants at risk Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Infections and infestations Upper respiratory tract infection	4.7% 10/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 5/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 7/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	6.6% 14/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 5/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 4/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	2.8% 6/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.4% 7/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.8% 6/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	5.6% 12/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.4% 7/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.8% 6/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 4/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 3/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 5/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	1.9% 4/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 6/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 5/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Sinusitis	2.3% 5/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 4/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 5/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	4.2% 9/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 6/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 2/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pain in extremity	2.3% 5/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 3/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 4/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	3.8% 8/213 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 4/207 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 2/104 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

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