Trial Outcomes & Findings for Efficacy and Safety of Alogliptin in Subjects With Type 2 Diabetes (NCT NCT00286455)

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

329 participants

Primary outcome timeframe

Baseline and Week 26.

Results posted on

2012-02-03

Participant Flow

Participants enrolled at 117 investigative sites in 16 countries from 24 February 2006 to 05 July 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 QD Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study STARTED	65	133	131
Overall Study COMPLETED	40	105	107
Overall Study NOT COMPLETED	25	28	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QD Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study Hyperglycemia rescue	19	13	10
Overall Study Adverse Event	1	3	2
Overall Study Lost to Follow-up	0	3	3
Overall Study Physician Decision	3	0	2
Overall Study Protocol Violation	1	1	0
Overall Study Participant Non-compliance	1	0	0
Overall Study Withdrawal by Subject	0	8	7

Baseline Characteristics

Efficacy and Safety of Alogliptin in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QD n=65 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.	Total n=329 Participants Total of all reporting groups
Age, Customized <65 years	53 participants n=5 Participants	110 participants n=7 Participants	111 participants n=5 Participants	274 participants n=4 Participants
Age, Customized Between 65 and 74 years	8 participants n=5 Participants	18 participants n=7 Participants	16 participants n=5 Participants	42 participants n=4 Participants
Age, Customized ≥75 years	4 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	13 participants n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	68 Participants n=7 Participants	54 Participants n=5 Participants	154 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	65 Participants n=7 Participants	77 Participants n=5 Participants	175 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26.

Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at the week 26 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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=128 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.	-0.02 percentage of Glycosylated Hemoglobin Standard Error 0.094	-0.56 percentage of Glycosylated Hemoglobin Standard Error 0.065	-0.59 percentage of Glycosylated Hemoglobin Standard Error 0.066

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=120 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 4).	-0.11 percentage of Glycosylated Hemoglobin Standard Error 0.052	-0.37 percentage of Glycosylated Hemoglobin Standard Error 0.035	-0.45 percentage of Glycosylated Hemoglobin Standard Error 0.036

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=128 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 8).	-0.13 percentage of Glycosylated Hemoglobin Standard Error 0.072	-0.53 percentage of Glycosylated Hemoglobin Standard Error 0.049	-0.64 percentage of Glycosylated Hemoglobin Standard Error 0.050

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=128 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 12).	-0.13 percentage of Glycosylated Hemoglobin Standard Error 0.080	-0.57 percentage of Glycosylated Hemoglobin Standard Error 0.055	-0.66 percentage of Glycosylated Hemoglobin Standard Error 0.056

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=128 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 16).	-0.12 percentage of Glycosylated Hemoglobin Standard Error 0.085	-0.59 percentage of Glycosylated Hemoglobin Standard Error 0.058	-0.65 percentage of Glycosylated Hemoglobin Standard Error 0.059

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=128 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (Week 20).	-0.12 percentage of Glycosylated Hemoglobin Standard Error 0.090	-0.58 percentage of Glycosylated Hemoglobin Standard Error 0.062	-0.61 percentage of Glycosylated Hemoglobin Standard Error 0.062

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 QD n=60 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=121 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 1).	4.6 mg/dL Standard Error 3.45	-8.6 mg/dL Standard Error 2.41	-14.0 mg/dL Standard Error 2.41

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 QD n=62 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=126 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 2).	3.8 mg/dL Standard Error 3.47	-14.6 mg/dL Standard Error 2.38	-17.6 mg/dL Standard Error 2.42

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=129 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 4).	2.8 mg/dL Standard Error 3.63	-15.6 mg/dL Standard Error 2.51	-21.6 mg/dL Standard Error 2.54

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 plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=131 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=129 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 8).	2.5 mg/dL Standard Error 4.20	-14.3 mg/dL Standard Error 2.91	-19.8 mg/dL Standard Error 2.94

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=132 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=129 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 12).	1.2 mg/dL Standard Error 4.29	-15.3 mg/dL Standard Error 2.97	-20.0 mg/dL Standard Error 3.01

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=132 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=129 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 16).	5.2 mg/dL Standard Error 4.64	-14.6 mg/dL Standard Error 3.21	-18.2 mg/dL Standard Error 3.25

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=132 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=129 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 20).	7.0 mg/dL Standard Error 4.73	-12.3 mg/dL Standard Error 3.27	-17.3 mg/dL Standard Error 3.31

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=132 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (Week 26).	11.3 mg/dL Standard Error 5.24	-10.3 mg/dL Standard Error 3.62	-16.4 mg/dL Standard Error 3.67

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 at any measurement time point during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=130 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).	30 participants	44 participants	33 participants

SECONDARY outcome

Timeframe: 26 Weeks.

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

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants Requiring Rescue.	19 participants	13 participants	10 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 QD n=57 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=117 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 4).	2.9 pmol/L Standard Error 3.24	-4.7 pmol/L Standard Error 2.22	-10.4 pmol/L Standard Error 2.24

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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 8).	-3.9 pmol/L Standard Error 3.60	-3.1 pmol/L Standard Error 2.46	-1.4 pmol/L Standard Error 2.51

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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 12).	-2.8 pmol/L Standard Error 3.10	-3.2 pmol/L Standard Error 2.11	-8.5 pmol/L Standard Error 2.16

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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 16).	-0.6 pmol/L Standard Error 3.42	-4.5 pmol/L Standard Error 2.33	-6.6 pmol/L Standard Error 2.38

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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 20).	-0.8 pmol/L Standard Error 2.75	-6.0 pmol/L Standard Error 1.87	-6.3 pmol/L Standard Error 1.91

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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin (Week 26).	-2.1 pmol/L Standard Error 2.87	-6.1 pmol/L Standard Error 1.96	-7.4 pmol/L Standard Error 2.00

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 QD n=55 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=117 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 4).	0.87 ϻIU/mL Standard Error 1.430	0.14 ϻIU/mL Standard Error 0.965	-1.27 ϻIU/mL Standard Error 0.973

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 insulin collected at week 8 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 8).	-0.35 ϻIU/mL Standard Error 1.520	1.18 ϻIU/mL Standard Error 1.023	0.94 ϻIU/mL Standard Error 1.042

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

Outcome measures

Outcome measures
Measure	Placebo QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 12).	-1.66 ϻIU/mL Standard Error 1.467	0.94 ϻIU/mL Standard Error 0.984	-1.60 ϻIU/mL Standard Error 1.006

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 16).	-0.41 ϻIU/mL Standard Error 1.577	0.55 ϻIU/mL Standard Error 1.058	-1.46 ϻIU/mL Standard Error 1.082

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 20).	-1.32 ϻIU/mL Standard Error 1.264	-0.32 ϻIU/mL Standard Error 0.847	-1.12 ϻIU/mL Standard Error 0.867

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 insulin collected at week 26 and insulin collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin (Week 26).	-1.17 ϻIU/mL Standard Error 1.404	-0.92 ϻIU/mL Standard Error 0.942	-1.08 ϻIU/mL Standard Error 0.963

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 QD n=55 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=117 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 4).	0.008 ratio Standard Error 0.0140	-0.043 ratio Standard Error 0.0094	-0.063 ratio Standard Error 0.0095

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 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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 8).	0.014 ratio Standard Error 0.0130	-0.054 ratio Standard Error 0.0087	-0.038 ratio Standard Error 0.0089

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 12).	0.025 ratio Standard Error 0.0150	-0.043 ratio Standard Error 0.0100	-0.047 ratio Standard Error 0.0103

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 16).	0.001 ratio Standard Error 0.0162	-0.044 ratio Standard Error 0.0109	-0.039 ratio Standard Error 0.0111

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 20).	0.119 ratio Standard Error 0.0393	-0.043 ratio Standard Error 0.0263	-0.040 ratio Standard Error 0.0270

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=124 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio (Week 26).	0.046 ratio Standard Error 0.0219	-0.040 ratio Standard Error 0.0147	-0.038 ratio Standard Error 0.0150

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 QD n=59 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=120 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 4).	0.242 ng/mL Standard Error 0.1467	0.026 ng/mL Standard Error 0.1024	0.088 ng/mL Standard Error 0.1023

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 C-peptide collected at week 8 and C-peptide collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=127 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 8).	-0.014 ng/mL Standard Error 0.1801	0.070 ng/mL Standard Error 0.1249	0.269 ng/mL Standard Error 0.1263

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=127 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 12).	-0.104 ng/mL Standard Error 0.1673	0.064 ng/mL Standard Error 0.1156	-0.091 ng/mL Standard Error 0.1173

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=127 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 16).	-0.030 ng/mL Standard Error 0.1712	-0.060 ng/mL Standard Error 0.1183	-0.127 ng/mL Standard Error 0.1200

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=127 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 20).	-0.194 ng/mL Standard Error 0.1288	-0.264 ng/mL Standard Error 0.0890	-0.231 ng/mL Standard Error 0.0903

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=127 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide (Week 26).	-0.282 ng/mL Standard Error 0.1387	-0.360 ng/mL Standard Error 0.0958	-0.279 ng/mL Standard Error 0.0973

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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.	7 participants	23 participants	27 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 7.0% during the 26 week study.

Outcome measures

Outcome measures
Measure	Placebo QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.	15 participants	63 participants	58 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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.	25 participants	81 participants	88 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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.	19 participants	67 participants	72 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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.	7 participants	38 participants	39 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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.	3 participants	11 participants	16 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 QD n=64 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=131 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.	1 participants	3 participants	6 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 timepoint 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 QD n=61 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=123 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 8).	-0.36 kg Standard Error 0.232	0.01 kg Standard Error 0.160	-0.03 kg Standard Error 0.162

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=125 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 12).	-0.25 kg Standard Error 0.257	-0.37 kg Standard Error 0.180	0.05 kg Standard Error 0.181

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=125 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 20).	-0.17 kg Standard Error 0.305	-0.18 kg Standard Error 0.213	-0.17 kg Standard Error 0.215

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 QD n=63 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=125 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight (Week 26).	0.18 kg Standard Error 0.368	-0.09 kg Standard Error 0.258	-0.22 kg Standard Error 0.259

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 glucagon collected at week 4 and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=45 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=101 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=91 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 4).	2.1 pg/mL Standard Deviation 2.51	3.6 pg/mL Standard Deviation 1.65	1.8 pg/mL Standard Deviation 1.75

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 glucagon collected at week 8 and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=50 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=109 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=100 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 8).	-1.2 pg/mL Standard Deviation 2.38	-0.9 pg/mL Standard Deviation 1.59	-0.2 pg/mL Standard Deviation 1.66

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 glucagon collected at week 12 and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=50 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=101 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 12).	-1.2 pg/mL Standard Deviation 2.30	0.8 pg/mL Standard Deviation 1.52	2.8 pg/mL Standard Deviation 1.60

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 glucagon collected at week 16 and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=50 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=101 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 16).	2.4 pg/mL Standard Deviation 2.53	3.3 pg/mL Standard Deviation 1.67	3.4 pg/mL Standard Deviation 1.76

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 glucagon collected at week 20 and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=50 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=101 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 20).	1.6 pg/mL Standard Deviation 2.50	3.3 pg/mL Standard Deviation 1.65	3.5 pg/mL Standard Deviation 1.74

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 glucagon collected at week 26 or final visit and glucagon collected at baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=50 Participants Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=101 Participants Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Glucagon (Week 26).	5.2 pg/mL Standard Deviation 2.66	4.2 pg/mL Standard Deviation 1.76	2.4 pg/mL Standard Deviation 1.85

Adverse Events

Placebo QD

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Alogliptin 12.5 mg QD

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Alogliptin 25 mg QD

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo QD n=64 participants at risk Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 mg QD n=133 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 mg QD n=132 participants at risk Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.
Cardiac disorders Angina pectoris	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.00% 0/133 • 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 event) after the last dose of double-blind 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.	0.76% 1/132 • 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 event) after the last dose of double-blind 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.
Cardiac disorders Palpitations	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.75% 1/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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 Irritable bowel syndrome	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.75% 1/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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 Noncardiac chest pain	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.75% 1/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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 Gastroenteritis	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.75% 1/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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 Pneumonia	1.6% 1/64 • 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 event) after the last dose of double-blind 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.	0.00% 0/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.6% 1/64 • 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 event) after the last dose of double-blind 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.	0.00% 0/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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 Intermittent claudication	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.00% 0/133 • 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 event) after the last dose of double-blind 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.	0.76% 1/132 • 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 event) after the last dose of double-blind 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 Peripheral vascular disorder	0.00% 0/64 • 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 event) after the last dose of double-blind 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.	0.75% 1/133 • 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 event) after the last dose of double-blind 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.	0.00% 0/132 • 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 event) after the last dose of double-blind 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.

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