Trial Outcomes & Findings for Efficacy and Safety of Alogliptin and Metformin Fixed-Dose Combination in Participants With Type 2 Diabetes (NCT NCT01890122)

Last Updated: 2016-11-28

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 early termination relative to baseline. Negative change indicates better glycemic control.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

647 participants

Primary outcome timeframe

Baseline and Week 26 (or Early termination)

Results posted on

2016-11-28

Participant Flow

Participants took part in the study at 59 investigative sites in China, Malaysia, South Korea and Taiwan from 26 August 2013 to 05 October 2015.

Participants with a diagnosis of type 2 diabetes mellitus were enrolled equally in 1 of 4 treatment groups, twice a day placebo, alogliptin 12.5 mg, metformin hydrochloride (HCl) 500 mg, or alogliptin 12.5 mg and metformin HCl 500 mg fixed dose combination (FDC).

Participant milestones

Participant milestones
Measure	Metformin HCl 500 mg Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Overall Study STARTED	162	163	159	163
Overall Study Treated	161	162	159	163
Overall Study COMPLETED	135	126	146	104
Overall Study NOT COMPLETED	27	37	13	59

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin HCl 500 mg Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Overall Study Adverse Event	1	1	1	2
Overall Study Major Protocol Deviation	3	1	0	1
Overall Study Lost to Follow-up	0	1	2	2
Overall Study Voluntary Withdrawal	8	8	2	11
Overall Study Lack of Efficacy	14	24	7	41
Overall Study Reason not Specified	0	1	1	2
Overall Study Randomized but not Treated	1	1	0	0

Baseline Characteristics

Efficacy and Safety of Alogliptin and Metformin Fixed-Dose Combination in Participants With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin HCl 500 mg n=162 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=163 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=159 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=163 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Total n=647 Participants Total of all reporting groups
Age, Continuous	53.6 years STANDARD_DEVIATION 9.91 • n=5 Participants	55.4 years STANDARD_DEVIATION 9.62 • n=7 Participants	53.4 years STANDARD_DEVIATION 10.46 • n=5 Participants	52.2 years STANDARD_DEVIATION 10.17 • n=4 Participants	53.6 years STANDARD_DEVIATION 10.08 • n=21 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	65 Participants n=7 Participants	68 Participants n=5 Participants	68 Participants n=4 Participants	281 Participants n=21 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	98 Participants n=7 Participants	91 Participants n=5 Participants	95 Participants n=4 Participants	366 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity, Customized Asian	161 participants n=5 Participants	162 participants n=7 Participants	159 participants n=5 Participants	161 participants n=4 Participants	643 participants n=21 Participants
Race/Ethnicity, Customized Multiracial	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino (Yes)	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino (No)	162 participants n=5 Participants	163 participants n=7 Participants	158 participants n=5 Participants	163 participants n=4 Participants	646 participants n=21 Participants
Height	163.8 cm STANDARD_DEVIATION 8.72 • n=5 Participants	165.0 cm STANDARD_DEVIATION 8.06 • n=7 Participants	164.3 cm STANDARD_DEVIATION 7.66 • n=5 Participants	164.2 cm STANDARD_DEVIATION 9.19 • n=4 Participants	164.3 cm STANDARD_DEVIATION 8.42 • n=21 Participants
Weight	70.79 kg STANDARD_DEVIATION 12.357 • n=5 Participants	71.21 kg STANDARD_DEVIATION 11.669 • n=7 Participants	70.73 kg STANDARD_DEVIATION 11.489 • n=5 Participants	71.79 kg STANDARD_DEVIATION 13.949 • n=4 Participants	71.13 kg STANDARD_DEVIATION 12.388 • n=21 Participants
Body Mass Index (BMI)	26.30 kg/m^2 STANDARD_DEVIATION 3.566 • n=5 Participants	26.16 kg/m^2 STANDARD_DEVIATION 3.923 • n=7 Participants	26.16 kg/m^2 STANDARD_DEVIATION 3.508 • n=5 Participants	26.56 kg/m^2 STANDARD_DEVIATION 4.218 • n=4 Participants	26.30 kg/m^2 STANDARD_DEVIATION 3.811 • n=21 Participants
Smoking Classification Has Never Smoked	125 participants n=5 Participants	112 participants n=7 Participants	113 participants n=5 Participants	112 participants n=4 Participants	462 participants n=21 Participants
Smoking Classification Is a Current Smoker	27 participants n=5 Participants	35 participants n=7 Participants	38 participants n=5 Participants	36 participants n=4 Participants	136 participants n=21 Participants
Smoking Classification Is an Ex-smoker	10 participants n=5 Participants	16 participants n=7 Participants	8 participants n=5 Participants	15 participants n=4 Participants	49 participants n=21 Participants
Female Reproductive Status Postmenopausal	47 participants n=5 Participants	45 participants n=7 Participants	37 participants n=5 Participants	45 participants n=4 Participants	174 participants n=21 Participants
Female Reproductive Status Surgically Sterile	8 participants n=5 Participants	8 participants n=7 Participants	10 participants n=5 Participants	5 participants n=4 Participants	31 participants n=21 Participants
Female Reproductive Status Female of Childbearing Potential	25 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants	18 participants n=4 Participants	76 participants n=21 Participants
Female Reproductive Status Not Applicable (Participant is Male)	82 participants n=5 Participants	98 participants n=7 Participants	91 participants n=5 Participants	95 participants n=4 Participants	366 participants n=21 Participants
Region of Enrollment China	129 participants n=5 Participants	129 participants n=7 Participants	128 participants n=5 Participants	130 participants n=4 Participants	516 participants n=21 Participants
Region of Enrollment Korea, Republic of	9 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	39 participants n=21 Participants
Region of Enrollment Malaysia	19 participants n=5 Participants	19 participants n=7 Participants	18 participants n=5 Participants	19 participants n=4 Participants	75 participants n=21 Participants
Region of Enrollment Taiwan, Province of China	5 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	17 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26 (or Early termination)

Population: Full analysis set consisted of all randomized participants in the safety set (participants who received at least 1 dose of study drug) who had baseline and at least 1 post baseline assessment. Last observation carried forward (LOCF) imputation was utilized.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=160 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=160 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=157 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 (or Early Termination)	-0.32 percentage of glycosylated hemoglobin Standard Deviation 1.067	-1.23 percentage of glycosylated hemoglobin Standard Deviation 0.877	-1.06 percentage of glycosylated hemoglobin Standard Deviation 0.970	-1.72 percentage of glycosylated hemoglobin Standard Deviation 1.024

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16 and 20

Population: Full analysis set consisted of all randomized participants in the safety set (participants who received at least 1 dose of study drug) who had baseline and at least 1 post baseline assessment. LOCF imputation was utilized. "n" in the category is the number of participants with data available at the given time-point.

The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Weeks 4, 8, 12, 16 and 20 relative to baseline. Negative change indicates better glycemic control.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20 Week 4 (n=157,156,154,156)	-0.57 percentage of glycosylated hemoglobin Standard Deviation 0.483	-0.41 percentage of glycosylated hemoglobin Standard Deviation 0.570	-0.80 percentage of glycosylated hemoglobin Standard Deviation 0.489	-0.18 percentage of glycosylated hemoglobin Standard Deviation 0.503
Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20 Week 8 (n=160,160,158,157)	-0.90 percentage of glycosylated hemoglobin Standard Deviation 0.682	-0.78 percentage of glycosylated hemoglobin Standard Deviation 0.756	-1.29 percentage of glycosylated hemoglobin Standard Deviation 0.732	-0.29 percentage of glycosylated hemoglobin Standard Deviation 0.738
Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20 Week 12 (n=160,160,158,157)	-1.06 percentage of glycosylated hemoglobin Standard Deviation 0.793	-1.01 percentage of glycosylated hemoglobin Standard Deviation 0.839	-1.57 percentage of glycosylated hemoglobin Standard Deviation 0.873	-0.27 percentage of glycosylated hemoglobin Standard Deviation 0.895
Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20 Week 16 (n=160,160,158,157)	-1.18 percentage of glycosylated hemoglobin Standard Deviation 0.816	-1.06 percentage of glycosylated hemoglobin Standard Deviation 0.900	-1.71 percentage of glycosylated hemoglobin Standard Deviation 0.937	-0.33 percentage of glycosylated hemoglobin Standard Deviation 0.957
Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20 Week 20 (n=160.160,158,157)	-1.24 percentage of glycosylated hemoglobin Standard Deviation 0.852	-1.11 percentage of glycosylated hemoglobin Standard Deviation 0.925	-1.74 percentage of glycosylated hemoglobin Standard Deviation 0.969	-0.33 percentage of glycosylated hemoglobin Standard Deviation 1.006

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26

Population: Full analysis set consisted of all randomized participants in the safety set (participants who received at least 1 dose of study drug) who had baseline and at least 1 post baseline assessment. LOCF imputation was utilized. "n" in the category is the number of participants with data available at the given time-point.

The change between the FPG value collected at Weeks 4, 8, 12, 16, 20 and 26 relative to baseline. Negative change indicates better glycemic control.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 16 (n=160,158,158,157)	-1.62 mg/dL Standard Deviation 1.599	-1.25 mg/dL Standard Deviation 2.148	-2.17 mg/dL Standard Deviation 1.923	-0.07 mg/dL Standard Deviation 2.020
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 4 (n=157,154,155,156)	-1.42 mg/dL Standard Deviation 1.344	-1.01 mg/dL Standard Deviation 1.794	-2.01 mg/dL Standard Deviation 2.157	0.02 mg/dL Standard Deviation 1.532
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 8 (n=160,158,158,157)	-1.50 mg/dL Standard Deviation 1.571	-1.17 mg/dL Standard Deviation 1.788	-2.13 mg/dL Standard Deviation 1.808	-0.08 mg/dL Standard Deviation 1.682
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 12 (n=160,158,158,157)	-1.48 mg/dL Standard Deviation 1.527	-1.33 mg/dL Standard Deviation 1.938	-2.14 mg/dL Standard Deviation 1.779	-0.08 mg/dL Standard Deviation 2.112
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 20 (n=160,158,158,157)	-1.57 mg/dL Standard Deviation 1.634	-1.19 mg/dL Standard Deviation 2.248	-2.26 mg/dL Standard Deviation 1.995	-0.12 mg/dL Standard Deviation 2.092
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26 Week 26 (n=160,158,158,157)	-1.45 mg/dL Standard Deviation 1.674	-1.06 mg/dL Standard Deviation 2.307	-2.06 mg/dL Standard Deviation 2.274	-0.04 mg/dL Standard Deviation 2.060

SECONDARY outcome

Timeframe: From the date of randomization through Week 26

Population: Randomized set consisted of all enrolled participants who were randomized.

Rescue is defined as meeting one of the following criteria, confirmed by a second sample drawn within 7 days of first sample: After \>1 week of treatment but prior to Week 4 visit: A single FPG ≥275 mg/dL (≥15.27 mmol/L); From the Week 4 but prior to the Week 8 visit: A single FPG ≥250 mg/dL (≥13.88 mmol/L); From the Week 8 visit but prior to the Week 12 visit: A single FPG ≥225 mg/dL (≥12.49 mmol/L); From the Week 12 visit through the end-of-treatment visit (week 26): HbA1c ≥8.5% and ≤0.5% reduction in HbA1c from baseline. Time to hyperglycemic rescue was censored if the participant did not experience a hyperglycemic rescue event.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=162 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=159 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=163 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Time to Hyperglycemic Rescue Event	NA days Data was not estimable as fewer than 50% of participants in any arm required hyperglycemic rescue.	NA days Data was not estimable as fewer than 50% of participants in any arm required hyperglycemic rescue.	NA days Data was not estimable as fewer than 50% of participants in any arm required hyperglycemic rescue.	NA days Interval 113.0 to Data was not estimable as fewer than 50% of participants in any arm required hyperglycemic rescue.

SECONDARY outcome

Timeframe: Baseline up to Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants Requiring Hyperglycemic Rescue	8.7 percentage of participants	14.8 percentage of participants	4.4 percentage of participants	25.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 26

Marked hyperglycemia is defined as FPG level ≥200 mg/dL (11.1 mmol/L).

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With Marked Hyperglycemia	8.8 percentage of participants	12.7 percentage of participants	5.7 percentage of participants	15.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set consisted of all randomized participants in the safety set (participants who received at least 1 dose of study drug) who had baseline and at least 1 post baseline assessment. LOCF imputation was utilized. "n" in the category is the number of participants with data available at the given time-point.

Change in participant's body weight at Weeks 12 and 26 relative to baseline.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=158 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Change From Baseline in Body Weight at Weeks 12 and 26 Week 12 (n=153,151,149,145)	-0.71 kg Standard Deviation 1.735	-0.19 kg Standard Deviation 1.696	-0.14 kg Standard Deviation 1.730	-0.32 kg Standard Deviation 1.837
Change From Baseline in Body Weight at Weeks 12 and 26 Week 26 (n=156,156,156,152)	-0.93 kg Standard Deviation 2.240	-0.22 kg Standard Deviation 2.291	-0.57 kg Standard Deviation 2.336	-0.33 kg Standard Deviation 2.220

SECONDARY outcome

Timeframe: Week 26

Clinical response at Week 26 will be assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) ≤6.5%.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤6.5%	27.3 percentage of participants	21.6 percentage of participants	55.1 percentage of participants	11.8 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤7.0%	55.9 percentage of participants	44.4 percentage of participants	77.2 percentage of participants	30.4 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤7.5%	73.3 percentage of participants	60.5 percentage of participants	84.8 percentage of participants	46.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Clinical response at Week 26 will be assessed by the percentage of participants with a decrease from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) of ≥0.5%.

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥0.5%	81.4 percentage of participants	74.1 percentage of participants	89.2 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥1.0%	63.4 percentage of participants	53.7 percentage of participants	83.5 percentage of participants	25.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥1.5%	37.3 percentage of participants	36.4 percentage of participants	62.0 percentage of participants	14.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Outcome measures

Outcome measures
Measure	Metformin HCl 500 mg n=161 Participants Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 Participants Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 Participants Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 Participants Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥2.0%	17.4 percentage of participants	17.3 percentage of participants	34.8 percentage of participants	6.2 percentage of participants

Adverse Events

Metformin HCl 500 mg

Serious events: 5 serious events

Other events: 33 other events

Deaths: 0 deaths

Alogliptin 12.5 mg

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Alogliptin 12.5 mg + Metformin HCl 500 mg FDC

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Metformin HCl 500 mg n=161 participants at risk Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg n=162 participants at risk Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.	Alogliptin 12.5 mg + Metformin HCl 500 mg FDC n=158 participants at risk Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.	Placebo n=161 participants at risk Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.
Gastrointestinal disorders Diarrhoea	3.1% 5/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	2.5% 4/162 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	0.63% 1/158 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	2.5% 4/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.
Infections and infestations Upper respiratory tract infection	6.8% 11/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	4.9% 8/162 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	5.1% 8/158 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	5.6% 9/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.
Infections and infestations Nasopharyngitis	3.7% 6/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	1.9% 3/162 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	1.3% 2/158 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	3.7% 6/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.
Investigations Protein urine present	3.1% 5/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	1.2% 2/162 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	4.4% 7/158 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	3.7% 6/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.
Metabolism and nutrition disorders Hyperlipidaemia	3.7% 6/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	5.6% 9/162 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	4.4% 7/158 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.	6.2% 10/161 • Week 1 up to Week 28 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. Safety set, all participants who took at least 1 dose of double-blind study drug.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER