Trial Outcomes & Findings for Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes. (NCT NCT00655863)

Last Updated: 2013-05-27

Results Overview

The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

71 participants

Primary outcome timeframe

Baseline and Week 16.

Results posted on

2013-05-27

Participant Flow

Participants enrolled at 2 investigative sites in The Netherlands and Sweden from 16 July 2007 to 17 December 2009.

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

Participant milestones

Participant milestones
Measure	Placebo QD Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Overall Study STARTED	24	25	22
Overall Study COMPLETED	24	25	21
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QD Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.	Total n=71 Participants Total of all reporting groups
Age Continuous	59.1 years STANDARD_DEVIATION 6.23 • n=93 Participants	58.7 years STANDARD_DEVIATION 6.47 • n=4 Participants	59.1 years STANDARD_DEVIATION 6.94 • n=27 Participants	59.0 years STANDARD_DEVIATION 6.45 • n=483 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	10 Participants n=4 Participants	7 Participants n=27 Participants	21 Participants n=483 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	15 Participants n=4 Participants	15 Participants n=27 Participants	50 Participants n=483 Participants
Region of Enrollment Netherlands	9 participants n=93 Participants	10 participants n=4 Participants	9 participants n=27 Participants	28 participants n=483 Participants
Region of Enrollment Sweden	15 participants n=93 Participants	15 participants n=4 Participants	13 participants n=27 Participants	43 participants n=483 Participants
Race (NIH/OMB)	24 Participants n=93 Participants	25 Participants n=4 Participants	22 Participants n=27 Participants	71 Participants n=483 Participants
Weight	101.83 kg STANDARD_DEVIATION 11.989 • n=93 Participants	93.68 kg STANDARD_DEVIATION 10.816 • n=4 Participants	93.05 kg STANDARD_DEVIATION 13.160 • n=27 Participants	96.24 kg STANDARD_DEVIATION 12.471 • n=483 Participants
Height	178.3 cm STANDARD_DEVIATION 6.74 • n=93 Participants	173.9 cm STANDARD_DEVIATION 8.17 • n=4 Participants	172.8 cm STANDARD_DEVIATION 10.97 • n=27 Participants	175.0 cm STANDARD_DEVIATION 8.91 • n=483 Participants
Body Mass Index (BMI)	32.12 kg/m2 STANDARD_DEVIATION 3.997 • n=93 Participants	31.09 kg/m2 STANDARD_DEVIATION 4.196 • n=4 Participants	31.15 kg/m2 STANDARD_DEVIATION 3.503 • n=27 Participants	31.46 kg/m2 STANDARD_DEVIATION 3.898 • n=483 Participants
Diabetes duration	5.55 years STANDARD_DEVIATION 3.243 • n=93 Participants	6.40 years STANDARD_DEVIATION 3.622 • n=4 Participants	5.03 years STANDARD_DEVIATION 3.791 • n=27 Participants	5.69 years STANDARD_DEVIATION 3.548 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16.

Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward.

The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16.	-39.728 mg.h/dL Standard Error 48.2481	-346.957 mg.h/dL Standard Error 47.2251	-293.439 mg.h/dL Standard Error 51.1271

SECONDARY outcome

Timeframe: Baseline and Week 4.

The change in postprandial incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8h)) postdose at week 4 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=19 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4.	-16.291 mg.h/dL Standard Error 61.1286	-288.490 mg.h/dL Standard Error 65.4530	-279.116 mg.h/dL Standard Error 68.4947

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in postprandial incremental area under the plasma concentration-time curve for very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL2 cholesterol, VLDL2 triglycerides, chylomicron cholesterol, chylomicron triglycerides, intermediate-density lipoprotein (IDL) cholesterol, and IDL triglycerides from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL triglycerides Week 4 (n=23; n=21; n=19)	-9.488 mg.h/dL Standard Error 35.4108	-119.009 mg.h/dL Standard Error 37.0255	-98.758 mg.h/dL Standard Error 38.9818
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL triglycerides Week 16 (n=23; n=25; n=21)	25.194 mg.h/dL Standard Error 29.4896	-130.459 mg.h/dL Standard Error 28.2397	-85.709 mg.h/dL Standard Error 30.7867
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL cholesterol Week 4 (n=23; n=21; n=19)	-6.914 mg.h/dL Standard Error 4.3110	-14.760 mg.h/dL Standard Error 4.4843	-10.760 mg.h/dL Standard Error 4.7065
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL cholesterol Week 16 (n=23; n=25; n=21)	-4.561 mg.h/dL Standard Error 3.4790	-16.365 mg.h/dL Standard Error 3.3125	-8.747 mg.h/dL Standard Error 3.5984
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL 2 triglycerides Week 4 (n=23; n=20; n=19)	-5.221 mg.h/dL Standard Error 7.8102	-17.960 mg.h/dL Standard Error 8.3710	-8.687 mg.h/dL Standard Error 8.6678
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL 2 triglycerides Week 16 (n=23; n=25; n=21)	-24.280 mg.h/dL Standard Error 3.4497	-18.986 mg.h/dL Standard Error 3.3104	-23.061 mg.h/dL Standard Error 3.6369
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL 2 cholesterol Week 4 (n=23; n=20; n=19)	-2.396 mg.h/dL Standard Error 0.8474	-0.709 mg.h/dL Standard Error 0.9059	-1.073 mg.h/dL Standard Error 0.9345
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. VLDL 2 cholesterol Week 16 (n=23; n=25; n=21)	-2.190 mg.h/dL Standard Error 0.7833	-1.445 mg.h/dL Standard Error 0.7506	-1.232 mg.h/dL Standard Error 0.8217
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. Chylomicron triglycerides Week 4 (n=23; n=21; n=1	0.617 mg.h/dL Standard Error 26.1603	-115.093 mg.h/dL Standard Error 27.4280	-108.036 mg.h/dL Standard Error 28.6857
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. Chylomicron triglycerides Week 16(n=23;n=25; n=21)	-18.577 mg.h/dL Standard Error 15.2943	-136.626 mg.h/dL Standard Error 14.6683	-129.991 mg.h/dL Standard Error 15.9053
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. Chylomicron cholesterol Week 4 (n=23; n=21; n=19)	-0.091 mg.h/dL Standard Error 1.1845	-4.474 mg.h/dL Standard Error 1.2425	-3.628 mg.h/dL Standard Error 1.3039
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. Chylomicron cholesterol Week 16 (n=23; n=25; n=21)	-1.431 mg.h/dL Standard Error 0.6001	-5.566 mg.h/dL Standard Error 0.5769	-4.289 mg.h/dL Standard Error 0.6265
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. IDL triglycerides Week 4 (n=22; n=18; n=17)	14.667 mg.h/dL Standard Error 12.9991	-6.771 mg.h/dL Standard Error 14.3964	-4.410 mg.h/dL Standard Error 14.9182
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. IDL triglycerides Week 16 (n=22; n=23; n=19)	-0.313 mg.h/dL Standard Error 2.9265	-4.045 mg.h/dL Standard Error 2.8759	-4.533 mg.h/dL Standard Error 3.1885
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. IDL cholesterol Week 4 (n=22; n=18; n=17)	1.473 mg.h/dL Standard Error 1.5215	-0.808 mg.h/dL Standard Error 1.6835	0.195 mg.h/dL Standard Error 1.7328
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. IDL cholesterol Week 16 (n=22; n=23; n=19)	0.171 mg.h/dL Standard Error 0.6006	0.249 mg.h/dL Standard Error 0.5893	0.609 mg.h/dL Standard Error 0.6499

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

Postprandial incremental area under the curve changes for very-low-density lipoprotein (VLDL) Apo B-48, VLDL Apo B 100, VLDL2 Apo B-48, VLDL2 Apo B 100, chylomicron Apo B-48, chylomicron Apo B 100, and intermediate density lipoprotein (IDL) Apo B-48, IDL Apo B 100, and triglyceride-rich remnant (TRR) lipoproteins from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL apo B-48 Week 4 (n=19; n=12; n=15)	-0.020 mg.h/dL Standard Error 0.2902	-0.491 mg.h/dL Standard Error 0.3572	-0.312 mg.h/dL Standard Error 0.3180
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL apo B-48 Week 16 (n=19; n=16; n=16)	-0.055 mg.h/dL Standard Error 0.1956	-0.654 mg.h/dL Standard Error 0.2077	-0.266 mg.h/dL Standard Error 0.2044
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL apo B 100 Week 4 (n=19; n=12; n=15)	0.568 mg.h/dL Standard Error 2.2981	-2.670 mg.h/dL Standard Error 2.8906	-2.977 mg.h/dL Standard Error 2.5811
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL apo B 100 Week 16 (n=19; n=16; n=16)	-0.453 mg.h/dL Standard Error 1.8388	-6.967 mg.h/dL Standard Error 2.0109	-3.265 mg.h/dL Standard Error 2.0025
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL2 apo B-48 Week 4 (n=19; n=12; n=15)	-0.075 mg.h/dL Standard Error 0.0776	-0.101 mg.h/dL Standard Error 0.0969	-0.022 mg.h/dL Standard Error 0.0870
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL2 apo B-48 Week 16 (n=19; n=16; n=16)	-0.079 mg.h/dL Standard Error 0.0674	-0.175 mg.h/dL Standard Error 0.0732	0.002 mg.h/dL Standard Error 0.0737
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL2 apo B 100 Week 4 (n=19; n=12; n=15)	0.464 mg.h/dL Standard Error 1.1846	0.507 mg.h/dL Standard Error 1.4982	-0.781 mg.h/dL Standard Error 1.33287
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. VLDL2 apo B 100 Week 16 (n=19; n=16; n=16)	-1.155 mg.h/dL Standard Error 0.7985	-2.049 mg.h/dL Standard Error 0.8732	-1.793 mg.h/dL Standard Error 0.8707
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. Chylomicron apo B-48 Week 4 (n=19; n=12; n=14)	-0.051 mg.h/dL Standard Error 0.0236	-0.097 mg.h/dL Standard Error 0.0302	-0.071 mg.h/dL Standard Error 0.0272
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. Chylomicron apo B-48 Week 16 (n=19; n=16; n=16)	-0.051 mg.h/dL Standard Error 0.0180	-0.113 mg.h/dL Standard Error 0.0197	-0.084 mg.h/dL Standard Error 0.0191
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. Chylomicron apo B 100 Week 4(n=19; n=12; n=14)	-0.123 mg.h/dL Standard Error 0.0825	-0.417 mg.h/dL Standard Error 0.1041	-0.389 mg.h/dL Standard Error 0.0960
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. Chylomicron apo B 100 Week 16 (n=19; n=16; n=16)	-0.120 mg.h/dL Standard Error 0.0544	-0.419 mg.h/dL Standard Error 0.0594	-0.409 mg.h/dL Standard Error 0.0590
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. IDL apo B-48 Week 4 (n=18; n=10; n=13)	0.002 mg.h/dL Standard Error 0.1254	-0.247 mg.h/dL Standard Error 0.1707	-0.223 mg.h/dL Standard Error 0.1476
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. IDL apo B-48 Week 16 (n=18; n=14; n=14)	0.151 mg.h/dL Standard Error 0.1368	-0.188 mg.h/dL Standard Error 0.1580	0.021 mg.h/dL Standard Error 0.1561
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. IDL apo B 100 Week 4 (n=18; n=10; n=13)	0.952 mg.h/dL Standard Error 3.3778	-2.029 mg.h/dL Standard Error 4.5494	-2.769 mg.h/dL Standard Error 3.8565
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. IDL apo B 100 Week 16 (n=18; n=14; n=14)	4.181 mg.h/dL Standard Error 3.4923	-2.876 mg.h/dL Standard Error 3.9944	0.073 mg.h/dL Standard Error 3.8906
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. TRR lipoproteins Week 4 (n=24; n=21; n=19)	16.147 mg.h/dL Standard Error 5.6739	-1.071 mg.h/dL Standard Error 6.0930	-5.673 mg.h/dL Standard Error 6.4428
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. TRR lipoproteins Week 16 (n=24; n=25; n=21)	2.818 mg.h/dL Standard Error 3.1250	-12.719 mg.h/dL Standard Error 3.0884	-7.853 mg.h/dL Standard Error 3.3658

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

Postprandial changes over time at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 4: 1 hour postprandial (n=20; n=17; n=15)	0.52 pmol/L Standard Error 1.167	-5.48 pmol/L Standard Error 1.249	-4.88 pmol/L Standard Error 1.330
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 4: 2 hours postprandial (n=21; n=17; n=16)	0.92 pmol/L Standard Error 1.524	-2.93 pmol/L Standard Error 1.702	-6.41 pmol/L Standard Error 1.732
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 4: 3 hours postprandial (n=21; n=17; n=16)	1.20 pmol/L Standard Error 1.619	-2.08 pmol/L Standard Error 1.789	-3.61 pmol/L Standard Error 1.848
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 4: 4 hours postprandial (n=21; n=17; n=16)	1.76 pmol/L Standard Error 1.823	2.86 pmol/L Standard Error 2.027	-0.84 pmol/L Standard Error 2.077
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 4: 8 hours postprandial (n=19; n=16; n=16)	-1.01 pmol/L Standard Error 0.955	-0.38 pmol/L Standard Error 1.039	-0.72 pmol/L Standard Error 1.040
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 16: 1 hour postprandial (n=21 ; n=20; n=16)	-0.28 pmol/L Standard Error 1.304	-4.10 pmol/L Standard Error 1.326	-3.63 pmol/L Standard Error 1.462
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 16: 2 hours postprandial (n=21; n=21; n=17)	-3.59 pmol/L Standard Error 1.451	-3.75 pmol/L Standard Error 1.457	-3.75 pmol/L Standard Error 1.599
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 16: 3 hours postprandial (n=21; n=21; n=17)	-1.08 pmol/L Standard Error 1.206	-2.25 pmol/L Standard Error 1.202	-3.17 pmol/L Standard Error 1.326
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 16: 4 hours postprandial (n=21; n=21; n=17)	-0.64 pmol/L Standard Error 1.263	-1.88 pmol/L Standard Error 1.271	-1.83 pmol/L Standard Error 1.393
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) Week 16: 8 hours postprandial (n=21; n=21; n=17)	-1.36 pmol/L Standard Error 0.820	0.03 pmol/L Standard Error 0.819	-1.48 pmol/L Standard Error 0.910

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

Postprandial changes over time at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Postprandial Changes Over Time From Baseline for Glucose Week 4: 1 hour postprandial (n=24; n=21; n=19)	-5.957 mg/dL Standard Error 5.3970	-35.065 mg/dL Standard Error 5.7617	-65.905 mg/dL Standard Error 6.0315
Postprandial Changes Over Time From Baseline for Glucose Week 4: 2 hours postprandial (n=23; n=21; n=19)	-4.049 mg/dL Standard Error 5.9932	-24.721 mg/dL Standard Error 6.2299	-67.718 mg/dL Standard Error 6.5647
Postprandial Changes Over Time From Baseline for Glucose Week 4: 3 hours postprandial (n=24; n=21; n=18)	3.200 mg/dL Standard Error 6.3047	-19.367 mg/dL Standard Error 6.7356	-54.345 mg/dL Standard Error 7.2106
Postprandial Changes Over Time From Baseline for Glucose Week 4: 4 hours postprandial (n=24; n=21; n=19)	2.930 mg/dL Standard Error 5.3775	-13.907 mg/dL Standard Error 5.6699	-48.643 mg/dL Standard Error 6.0151
Postprandial Changes Over Time From Baseline for Glucose Week 4: 8 hours postprandial (n=22; n=21; n=19)	0.046 mg/dL Standard Error 4.1120	-6.077 mg/dL Standard Error 4.2043	-27.856 mg/dL Standard Error 4.3961
Postprandial Changes Over Time From Baseline for Glucose Week 16: 1 hour postprandial (n=24; n=25; n=21)	11.867 mg/dL Standard Error 8.1356	-36.189 mg/dL Standard Error 7.9793	-58.168 mg/dL Standard Error 8.6585
Postprandial Changes Over Time From Baseline for Glucose Week 16: 2 hours postprandial (n=23; n=25; n=21)	17.324 mg/dL Standard Error 8.6572	-29.745 mg/dL Standard Error 8.2830	-61.899 mg/dL Standard Error 9.0248
Postprandial Changes Over Time From Baseline for Glucose Week 16: 3 hours postprandial (n=24; n=25; n=20)	18.379 mg/dL Standard Error 7.8017	-16.996 mg/dL Standard Error 7.6465	-51.891 mg/dL Standard Error 8.4838
Postprandial Changes Over Time From Baseline for Glucose Week 16: 4 hours postprandial (n=24; n=25; n=21)	10.849 mg/dL Standard Error 7.3084	-12.517 mg/dL Standard Error 7.1054	-41.943 mg/dL Standard Error 7.7396
Postprandial Changes Over Time From Baseline for Glucose Week 16: 8 hours postprandial (n=24; n=25; n=21)	3.266 mg/dL Standard Error 5.0112	-5.737 mg/dL Standard Error 4.9335	-19.381 mg/dL Standard Error 5.3350

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

Postprandial changes over time at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Postprandial Changes Over Time From Baseline for Insulin Week 4: 1 hour postprandial (n=24; n=21; n=18)	-5.047 uIU/mL Standard Error 3.5562	-5.867 uIU/mL Standard Error 3.7749	-18.287 uIU/mL Standard Error 4.0906
Postprandial Changes Over Time From Baseline for Insulin Week 4: 2 hours postprandial (n=24; n=21; n=19)	1.405 uIU/mL Standard Error 6.3051	3.161 uIU/mL Standard Error 6.7294	-28.700 uIU/mL Standard Error 7.0572
Postprandial Changes Over Time From Baseline for Insulin Week 4: 3 hours postprandial (n=24; n=21; n=19)	0.637 uIU/mL Standard Error 5.2789	0.652 uIU/mL Standard Error 5.6125	-18.842 uIU/mL Standard Error 5.9301
Postprandial Changes Over Time From Baseline for Insulin Week 4: 4 hours postprandial (n=24; n=21; n=19)	2.999 uIU/mL Standard Error 3.5652	5.092 uIU/mL Standard Error 3.8075	-12.891 uIU/mL Standard Error 4.0088
Postprandial Changes Over Time From Baseline for Insulin Week 4: 8 hours postprandial (n=23; n=21; n=19)	-1.174 uIU/mL Standard Error 1.0270	2.685 uIU/mL Standard Error 1.0772	-6.000 uIU/mL Standard Error 1.1301
Postprandial Changes Over Time From Baseline for Insulin Week 16: 1 hour postprandial (n=24; n=25; n=21)	-8.896 uIU/mL Standard Error 4.8993	-14.368 uIU/mL Standard Error 4.7784	-12.162 uIU/mL Standard Error 5.2052
Postprandial Changes Over Time From Baseline for Insulin Week 16: 2 hours postprandial (n=24; n=25; n=21)	-9.258 uIU/mL Standard Error 6.5119	-9.528 uIU/mL Standard Error 6.4000	-24.777 uIU/mL Standard Error 6.9371
Postprandial Changes Over Time From Baseline for Insulin Week 16: 3 hours postprandial (n=24; n=25; n=21)	4.447 uIU/mL Standard Error 4.8889	-9.848 uIU/mL Standard Error 4.7800	-23.025 uIU/mL Standard Error 5.2049
Postprandial Changes Over Time From Baseline for Insulin Week 16: 4 hours postprandial (n=24; n=25; n=21)	8.405 uIU/mL Standard Error 4.5090	-4.753 uIU/mL Standard Error 4.4158	-19.329 uIU/mL Standard Error 4.8159
Postprandial Changes Over Time From Baseline for Insulin Week 16: 8 hours postprandial (n=24; n=25; n=21)	0.495 uIU/mL Standard Error 1.2847	3.163 uIU/mL Standard Error 1.2637	-6.107 uIU/mL Standard Error 1.3728

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

Postprandial changes over time at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Postprandial Changes Over Time From Baseline for Glucagon Week 4: 1 hour postprandial (n=24; n=21; n=19)	7.222 pg/mL Standard Error 3.7636	-14.639 pg/mL Standard Error 4.0619	-17.704 pg/mL Standard Error 4.2418
Postprandial Changes Over Time From Baseline for Glucagon Week 4: 2 hours postprandial (n=24; n=21; n=19)	1.730 pg/mL Standard Error 3.3262	-17.015 pg/mL Standard Error 3.5627	-22.081 pg/mL Standard Error 3.7541
Postprandial Changes Over Time From Baseline for Glucagon Week 4: 3 hours postprandial (n=24; n=21; n=19)	6.637 pg/mL Standard Error 3.7141	-13.200 pg/mL Standard Error 3.9753	-15.987 pg/mL Standard Error 4.2015
Postprandial Changes Over Time From Baseline for Glucagon Week 4: 4 hours postprandial (n=24; n=20; n=18)	2.021 pg/mL Standard Error 4.1496	-4.679 pg/mL Standard Error 4.5627	-8.860 pg/mL Standard Error 4.7910
Postprandial Changes Over Time From Baseline for Glucagon Week 4: 8 hours postprandial (n=22; n=20; n=19)	1.081 pg/mL Standard Error 3.5000	-3.789 pg/mL Standard Error 3.6665	-5.150 pg/mL Standard Error 3.7592
Postprandial Changes Over Time From Baseline for Glucagon Week 16: 1 hour postprandial (n=24; n=25; n=21)	3.318 pg/mL Standard Error 3.1819	-16.955 pg/mL Standard Error 3.1477	-17.462 pg/mL Standard Error 3.4144
Postprandial Changes Over Time From Baseline for Glucagon Week 16: 2 hours postprandial (n=24; n=25; n=21)	-1.047 pg/mL Standard Error 3.4159	-20.949 pg/mL Standard Error 3.3556	-20.662 pg/mL Standard Error 3.6653
Postprandial Changes Over Time From Baseline for Glucagon Week 16: 3 hours postprandial (n=24; n=25; n=21)	4.842 pg/mL Standard Error 3.4670	-13.602 pg/mL Standard Error 3.4048	10.84 pg/mL Standard Error 3.7260
Postprandial Changes Over Time From Baseline for Glucagon Week 16: 4 hours postprandial (n=24; n=24; n=21)	2.801 pg/mL Standard Error 3.1830	-8.577 pg/mL Standard Error 3.1873	-10.326 pg/mL Standard Error 3.4011
Postprandial Changes Over Time From Baseline for Glucagon Week 16: 8 hours postprandial (n=24; n=25; n=21)	3.917 pg/mL Standard Error 2.5383	-5.818 pg/mL Standard Error 2.4876	-9.332 pg/mL Standard Error 2.7108

SECONDARY outcome

Timeframe: Baseline, Week 8 and Week 16.

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Glycosylated Hemoglobin Week 8: fasting (n=23; n=24; n=20)	-0.12 percentage of glycosylated hemoglobin Standard Error 0.084	-0.55 percentage of glycosylated hemoglobin Standard Error 0.083	-1.01 percentage of glycosylated hemoglobin Standard Error 0.090
Change From Baseline in Glycosylated Hemoglobin Week 16: 5 minutes prior to meal (n=24;n=25; n=21)	0.38 percentage of glycosylated hemoglobin Standard Error 0.131	-0.39 percentage of glycosylated hemoglobin Standard Error 0.129	-0.95 percentage of glycosylated hemoglobin Standard Error 0.140

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8 and Week 16.

The change in fasting plasma glucose collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Fasting Plasma Glucose Week 4 (n=24; n=20; n=19)	-4.141 mg/dL Standard Error 3.0027	-20.669 mg/dL Standard Error 3.3024	-38.826 mg/dL Standard Error 3.3890
Change From Baseline in Fasting Plasma Glucose Week 8 (n=24; n=25; n=21)	4.864 mg/dL Standard Error 5.3254	-16.293 mg/dL Standard Error 5.2451	-38.242 mg/dL Standard Error 5.7203
Change From Baseline in Fasting Plasma Glucose Week 16 (n=24; n=25; n=21)	11.869 mg/dL Standard Error 6.4897	-17.052 mg/dL Standard Error 6.3918	-38.481 mg/dL Standard Error 6.9709

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in postprandial C-peptide collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial C-Peptide Week 4: 1 hour postprandial (n=24; n=21; n=19)	-0.106 ng/mL Standard Error 0.2597	-0.300 ng/mL Standard Error 0.2775	-1.199 ng/mL Standard Error 0.2921
Change From Baseline in Postprandial C-Peptide Week 4: 2 hours postprandial (n=24; n=21; n=19)	0.311 ng/mL Standard Error 0.3789	-0.011 ng/mL Standard Error 0.4052	-1.379 ng/mL Standard Error 0.4262
Change From Baseline in Postprandial C-Peptide Week 4: 3 hours postprandial (n=24; n=21; n=19)	0.376 ng/mL Standard Error 0.4386	0.116 ng/mL Standard Error 0.4684	-1.230 ng/mL Standard Error 0.4933
Change From Baseline in Postprandial C-Peptide Week 4: 4 hours postprandial (n=24; n=21; n=19)	0.256 ng/mL Standard Error 0.3674	0.393 ng/mL Standard Error 0.3926	-1.173 ng/mL Standard Error 0.4140
Change From Baseline in Postprandial C-Peptide Week 4: 8 hours postprandial (n=23; n=20; n=19)	-0.063 ng/mL Standard Error 0.1530	0.421 ng/mL Standard Error 0.1643	-0.911 ng/mL Standard Error 0.1699
Change From Baseline in Postprandial C-Peptide Week 16: 1 hour postprandial (n=24; n=25; n=21)	-0.176 ng/mL Standard Error 0.3474	-1.021 ng/mL Standard Error 0.3405	-0.646 ng/mL Standard Error 0.3712
Change From Baseline in Postprandial C-Peptide Week 16: 2 hours postprandial (n=24; n=25; n=21)	-0.011 ng/mL Standard Error 0.4337	-1.006 ng/mL Standard Error 0.4259	-1.055 ng/mL Standard Error 0.4638
Change From Baseline in Postprandial C-Peptide Week 16: 3 hours postprandial (n=24; n=25; n=21)	0.492 ng/mL Standard Error 0.4570	-0.712 ng/mL Standard Error 0.4478	-1.269 ng/mL Standard Error 0.4882
Change From Baseline in Postprandial C-Peptide Week 16: 4 hours postprandial (n=24; n=25; n=21)	0.496 ng/mL Standard Error 0.4042	-0.068 ng/mL Standard Error 0.3961	-1.515 ng/mL Standard Error 0.4323
Change From Baseline in Postprandial C-Peptide Week 16: 8 hours postprandial (n=24; n=24; n=21)	0.151 ng/mL Standard Error 0.2042	0.588 ng/mL Standard Error 0.2047	-0.761 ng/mL Standard Error 0.2194

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in postprandial proinsulin collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Postprandial Proinsulin Week 4: 1 hour postprandial (n=24; n=21; n=19)	-4.555 pmol/L Standard Error 3.9248	-13.024 pmol/L Standard Error 4.2068	-41.192 pmol/L Standard Error 4.4562
Change From Baseline in Postprandial Proinsulin Week 4: 2 hours postprandial (n=24; n=21; n=19)	-0.208 pmol/L Standard Error 5.5216	-12.568 pmol/L Standard Error 5.9505	-56.478 pmol/L Standard Error 6.3185
Change From Baseline in Postprandial Proinsulin Week 4: 3 hours postprandial (n=24; n=21; n=19)	-6.735 pmol/L Standard Error 5.9547	-12.987 pmol/L Standard Error 6.4485	-59.573 pmol/L Standard Error 6.8034
Change From Baseline in Postprandial Proinsulin Week 4: 4 hours postprandial (n=24; n=21; n=19)	-6.496 pmol/L Standard Error 5.9756	-6.848 pmol/L Standard Error 6.4875	-52.649 pmol/L Standard Error 6.8526
Change From Baseline in Postprandial Proinsulin Week 4: 8 hours postprandial (n=23; n=21; n=19)	-5.082 pmol/L Standard Error 4.3735	-5.561 pmol/L Standard Error 4.6395	-35.159 pmol/L Standard Error 4.9287
Change From Baseline in Postprandial Proinsulin Week 16: 1 hour postprandial (n=24; n=25; n=21)	2.081 pmol/L Standard Error 5.3253	-22.812 pmol/L Standard Error 5.2274	-30.658 pmol/L Standard Error 5.7287
Change From Baseline in Postprandial Proinsulin Week 16: 2 hours postprandial (n=24; n=25; n=21)	3.336 pmol/L Standard Error 6.3373	-29.930 pmol/L Standard Error 6.2396	-45.487 pmol/L Standard Error 6.8516
Change From Baseline in Postprandial Proinsulin Week 16: 3 hours postprandial (n=24; n=25; n=21)	5.863 pmol/L Standard Error 6.2769	-27.768 pmol/L Standard Error 6.2041	-50.058 pmol/L Standard Error 6.7783
Change From Baseline in Postprandial Proinsulin Week 16: 4 hours postprandial (n=24; n=25; n=21)	8.671 pmol/L Standard Error 5.7153	-21.862 pmol/L Standard Error 5.6549	-48.757 pmol/L Standard Error 6.1834
Change From Baseline in Postprandial Proinsulin Week 16: 8 hours postprandial (n=24; n=25; n=21)	6.935 pmol/L Standard Error 5.2859	-6.898 pmol/L Standard Error 5.2307	-28.776 pmol/L Standard Error 5.7372

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in hs-CRP collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) Week 4: 5 minutes prior to meal (n=24; n=21; n=19)	-1.514 mg/L Standard Error 1.0846	0.631 mg/L Standard Error 1.1693	0.155 mg/L Standard Error 1.2269
Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) Week 16: 5 minutes prior to meal (n=24; n=25;n=21)	4.338 mg/L Standard Error 2.6070	-0.402 mg/L Standard Error 2.5683	-0.402 mg/L Standard Error 2.8000

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in adiponectin collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Adiponectin Week 4: 5 minutes prior to meal (n=24;n=21; n=19)	0.001 µg/mL Standard Error 0.0004	0.000 µg/mL Standard Error 0.0005	0.006 µg/mL Standard Error 0.0005
Change From Baseline in Adiponectin Week 16: 5 minutes prior to meal (n=24;n=25;n=21)	0.000 µg/mL Standard Error 0.0005	0.000 µg/mL Standard Error 0.0005	0.007 µg/mL Standard Error 0.0005

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in VCAM collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) Week 16: 5 minutes prior to meal (n=24;n=25;n=21)	5.067 ng/mL Standard Error 16.6654	-1.441 ng/mL Standard Error 16.3094	13.665 ng/mL Standard Error 17.7580
Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) Week 4: 5 minutes prior to meal (n=24;n=21; n=19)	-37.351 ng/mL Standard Error 17.6828	2.392 ng/mL Standard Error 18.8767	4.849 ng/mL Standard Error 19.8297

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in ICAM collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=21 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) Week 4: 5 minutes prior to meal (n=24;n=21; n=19)	-1.154 ng/mL Standard Error 6.7415	-0.294 ng/mL Standard Error 7.1785	-23.810 ng/mL Standard Error 7.6380
Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) Week 16: 5 minutes prior to meal (n=24; n=25;n=21)	-2.495 ng/mL Standard Error 8.6653	-4.140 ng/mL Standard Error 8.4752	-16.556 ng/mL Standard Error 9.3414

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 16.

The change in e-Selectin collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in e-Selectin Week 16: 5 minutes prior to meal (n=24; n=25;n=21)	1.488 ng/mL Standard Error 2.0944	-1.671 ng/mL Standard Error 2.0480	-4.056 ng/mL Standard Error 2.2336
Change From Baseline in e-Selectin Week 4: 5 minutes prior to meal (n=24;n=21; n=19)	1.041 ng/mL Standard Error 1.3484	0.116 ng/mL Standard Error 1.4394	-6.437 ng/mL Standard Error 1.5137

SECONDARY outcome

Timeframe: Baseline and Week 16.

Pulse wave tonometry performed before the meal and 2 hours postmeal using one recording consisting of 15 to 20 sequentially recorded radial artery waveforms collected at each assessment.

Outcome measures

Outcome measures
Measure	Placebo QD n=24 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Change From Baseline in Endothelial Function Through Pulse Wave Tonometry Week 16: pre-meal (n=23;n=23;n=20)	-3.6 mmHg Standard Error 2.51	-4.7 mmHg Standard Error 2.52	-4.2 mmHg Standard Error 2.68
Change From Baseline in Endothelial Function Through Pulse Wave Tonometry Week 16: 2 hours postmeal (n=24;n=24;n=20)	-1.6 mmHg Standard Error 3.16	0.1 mmHg Standard Error 3.18	-1.3 mmHg Standard Error 3.47

Adverse Events

Placebo QD

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Alogliptin 25 mg QD

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Alogliptin 25 mg QD + Pioglitazone 30 mg QD

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo QD n=24 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD n=25 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.	Alogliptin 25 mg QD + Pioglitazone 30 mg QD n=22 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Gastrointestinal disorders Gastric ulcer	0.00% 0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/22 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Concussion	0.00% 0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.5% 1/22 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.5% 1/22 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Head injury	0.00% 0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.5% 1/22 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Nephrolithiasis	0.00% 0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 1/25 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/22 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG 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