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Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.

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ClinicalTrials.gov Identifier: NCT00328627
Recruitment Status : Completed
First Posted : May 22, 2006
Results First Posted : April 4, 2013
Last Update Posted : April 4, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Alogliptin
Drug: Alogliptin placebo
Drug: Pioglitazone
Drug: Pioglitazone placebo
Enrollment 1554
Recruitment Details Participants took part in the study at 327 investigative sites in 20 countries from 31 May 2006 to 17 March 2008.
Pre-assignment Details Participants with a diagnosis of type 2 diabetes who were inadequately controlled on a regimen of metformin alone were equally randomized to 1 of 12 double-blind treatment groups.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Period Title: Overall Study
Started 129 128 129 130 130 130 129 130 130 129 130 130
Safety Set 129 [1] 128 129 129 130 130 129 130 130 129 130 130
Completed 70 97 101 93 115 110 94 116 113 97 112 114
Not Completed 59 31 28 37 15 20 35 14 17 32 18 16
Reason Not Completed
Hyperglycemic Rescue             41             18             16             13             6             5             19             6             6             11             3             2
Adverse Event             3             1             2             3             1             2             1             2             0             7             5             4
Protocol Violation             2             2             2             8             5             5             6             2             1             4             6             2
Lost to Follow-up             4             2             2             4             0             2             3             0             3             2             0             1
Withdrawal by Subject             5             4             5             6             2             5             4             4             4             5             2             7
Pregnancy             0             1             0             0             0             0             0             0             0             0             0             0
Physician Decision             4             3             1             2             1             1             1             0             3             2             1             0
Other             0             0             0             1             0             0             1             0             0             1             1             0
[1]
All patients who took at least 1 dose of double-blind study drug.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45 Total
Hide Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks. Total of all reporting groups
Overall Number of Baseline Participants 129 128 129 130 130 130 129 130 130 129 130 130 1554
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
55.2  (9.89) 53.1  (9.59) 53.7  (9.31) 54.1  (9.54) 53.6  (9.91) 54.9  (9.18) 56.1  (9.43) 55.0  (9.07) 54.4  (9.69) 54.5  (9.70) 54.0  (9.82) 54.2  (8.86) 54.4  (9.50)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
<65 years 106 116 112 113 109 112 101 111 107 112 111 112 1322
≥65 years 23 12 17 17 21 18 28 19 23 17 19 18 232
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
Female
68
  52.7%
61
  47.7%
79
  61.2%
69
  53.1%
70
  53.8%
69
  53.1%
66
  51.2%
76
  58.5%
75
  57.7%
76
  58.9%
70
  53.8%
78
  60.0%
857
  55.1%
Male
61
  47.3%
67
  52.3%
50
  38.8%
61
  46.9%
60
  46.2%
61
  46.9%
63
  48.8%
54
  41.5%
55
  42.3%
53
  41.1%
60
  46.2%
52
  40.0%
697
  44.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
Hispanic or Latino
63
  48.8%
60
  46.9%
63
  48.8%
63
  48.5%
55
  42.3%
57
  43.8%
67
  51.9%
66
  50.8%
62
  47.7%
61
  47.3%
63
  48.5%
65
  50.0%
745
  47.9%
Not Hispanic or Latino
66
  51.2%
68
  53.1%
66
  51.2%
67
  51.5%
75
  57.7%
73
  56.2%
62
  48.1%
64
  49.2%
68
  52.3%
68
  52.7%
67
  51.5%
65
  50.0%
809
  52.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   1.5%
2
   1.5%
0
   0.0%
1
   0.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
   0.3%
Asian
5
   3.9%
14
  10.9%
15
  11.6%
11
   8.5%
9
   6.9%
7
   5.4%
10
   7.8%
5
   3.8%
12
   9.2%
12
   9.3%
8
   6.2%
12
   9.2%
120
   7.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
   6.2%
6
   4.7%
5
   3.9%
8
   6.2%
4
   3.1%
3
   2.3%
6
   4.7%
2
   1.5%
5
   3.8%
9
   7.0%
9
   6.9%
3
   2.3%
68
   4.4%
White
93
  72.1%
89
  69.5%
80
  62.0%
85
  65.4%
95
  73.1%
96
  73.8%
96
  74.4%
107
  82.3%
85
  65.4%
85
  65.9%
92
  70.8%
93
  71.5%
1096
  70.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
23
  17.8%
19
  14.8%
29
  22.5%
26
  20.0%
20
  15.4%
22
  16.9%
17
  13.2%
15
  11.5%
28
  21.5%
23
  17.8%
21
  16.2%
22
  16.9%
265
  17.1%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
83.38  (18.378) 84.63  (19.378) 83.25  (18.326) 84.68  (18.634) 85.95  (18.498) 82.90  (16.570) 85.86  (20.347) 83.68  (18.340) 85.77  (18.844) 82.10  (17.019) 85.01  (18.536) 82.79  (18.768) 84.17  (18.470)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
164.48  (10.157) 164.61  (10.614) 162.38  (9.790) 164.25  (11.007) 164.59  (10.841) 163.74  (10.456) 164.59  (9.724) 163.63  (11.036) 163.64  (9.548) 163.14  (10.961) 163.82  (10.708) 163.73  (11.432) 163.88  (10.522)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
30.59  (4.808) 30.96  (5.133) 31.48  (5.733) 31.25  (5.280) 31.53  (4.979) 30.78  (4.723) 31.41  (5.391) 31.09  (5.054) 31.86  (5.585) 30.69  (4.721) 31.51  (5.206) 30.62  (4.751) 31.15  (5.122)
Diabetes Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
6.01  (4.958) 6.17  (5.614) 5.55  (4.879) 5.70  (4.767) 6.08  (5.485) 6.86  (5.489) 7.63  (7.069) 5.81  (5.054) 6.63  (6.005) 5.68  (4.232) 6.59  (5.273) 6.22  (5.014) 6.24  (5.375)
Baseline metformin dose  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 129 participants 128 participants 129 participants 130 participants 130 participants 130 participants 129 participants 130 participants 130 participants 129 participants 130 participants 130 participants 1554 participants
1936.8  (428.41) 1902.0  (450.17) 1851.2  (413.85) 1892.6  (410.70) 1909.6  (418.98) 1880.0  (413.65) 1853.5  (435.72) 1822.3  (444.22) 1867.1  (455.48) 1918.6  (417.91) 1919.6  (421.22) 1884.6  (439.47) 1886.5  (429.08)
1.Primary Outcome
Title Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)
Hide Description

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).

Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:

Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).

This combination group includes participants from the following three treatment arms:

  1. Placebo + Pioglitazone 15 mg
  2. Placebo + Pioglitazone 30 mg
  3. Placebo + Pioglitazone 45 mg

Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).

This combination group includes participants from the following three treatment arms:

  1. Alogliptin 12.5 mg + Pioglitazone 15 mg
  2. Alogliptin 12.5 mg + Pioglitazone 30 mg
  3. Alogliptin 12.5 mg + Pioglitazone 45 mg

Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).

This combination group includes participants from the following three treatment arms:

  1. Alogliptin 25 mg + Pioglitazone 15 mg
  2. Alogliptin 25 mg + Pioglitazone 30 mg
  3. Alogliptin 25 mg + Pioglitazone 45 mg
Overall Number of Participants Analyzed 376 385 377
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.89  (0.046) -1.43  (0.046) -1.42  (0.046)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone Alone, Alogliptin 12.5 + Pioglitazone
Comments The null hypothesis was that the doses of alogliptin do not have any additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone. The alternative hypothesis was that at least the higher dose of alogliptin would have an additive effect on glycemic control (HbA1c) in addition to the effect produced by pioglitazone alone.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments For the primary analysis, the overall average HbA1c response of the Alogliptin/pioglitazone combination groups was compared with that of the pioglitazone alone groups at the 2-sided 0.05 significance level with no adjustment for multiple comparisons.
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.67 to -0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone Alone, Alogliptin 25 + Pioglitazone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-0.66 to -0.41
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline to Week 26 in HbA1c
Hide Description The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 126 122 123 127 130 127 123 128 124 126 127 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.13  (0.080) -0.64  (0.081) -0.90  (0.081) -0.75  (0.079) -1.34  (0.078) -1.27  (0.079) -0.92  (0.081) -1.39  (0.079) -1.39  (0.080) -1.00  (0.080) -1.55  (0.079) -1.60  (0.080)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 + Placebo, Alogliptin 12.5 + Pioglitazone 15
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments As a supportive analysis, each of the individual combination treatment groups was compared with the component treatment groups receiving aloliptin alone and pioglitazone alone at the 2-sided 0.05 significance level with no multiplicity adjustment.
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.70
Confidence Interval (2-Sided) 95%
-0.93 to -0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 15, Alogliptin 12.5 + Pioglitazone 15
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-0.81 to -0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 + Placebo, Alogliptin 25 + Pioglitazone 15
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.59 to -0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 15, Alogliptin 25 + Pioglitazone 15
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.74 to -0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 + Placebo, Alogliptin 12.5 + Pioglitazone 30
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.76
Confidence Interval (2-Sided) 95%
-0.98 to -0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 30, Alogliptin 12.5 + Pioglitazone 30
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.70 to -0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 + Placebo, Alogliptin 25 + Pioglitazone 30
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.71 to -0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 30, Alogliptin 25 + Pioglitazone 30
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.70 to -0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 + Placebo, Alogliptin 12.5 + Pioglitazone 45
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-1.13 to -0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 45, Alogliptin 12.5 + Pioglitazone 45
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.55
Confidence Interval (2-Sided) 95%
-0.77 to -0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 + Placebo, Alogliptin 25 + Pioglitazone 45
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.70
Confidence Interval (2-Sided) 95%
-0.92 to -0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo + Pioglitazone 45, Alogliptin 25 + Pioglitazone 45
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-0.83 to -0.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in HbA1c Over Time (Grouped Analysis)
Hide Description

The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.

Time Frame Baseline and Weeks 4, 8, 12, 16 and 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
Week 4 (n=345, 359, 346) -0.32  (0.023) -0.57  (0.023) -0.61  (0.023)
Week 8 (n=376, 385, 377) -0.61  (0.034) -1.06  (0.033) -1.09  (0.034)
Week 12 (n=376, 385, 377) -0.81  (0.039) -1.29  (0.039) -1.38  (0.039)
Week 16 (n=376, 385, 377) -0.92  (0.041) -1.44  (0.041) -1.49  (0.041)
Week 20 (n=376, 385, 377) -0.92  (0.043) -1.46  (0.042) -1.51  (0.043)
4.Secondary Outcome
Title Change From Baseline to Week 4 in HbA1c
Hide Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 120 114 110 114 120 116 116 122 118 115 117 112
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.22  (0.039) -0.46  (0.040) -0.51  (0.041) -0.32  (0.040) -0.53  (0.039) -0.61  (0.040) -0.24  (0.040) -0.60  (0.039) -0.60  (0.039) -0.40  (0.040) -0.58  (0.040) -0.63  (0.040)
5.Secondary Outcome
Title Change From Baseline to Week 8 in HbA1c
Hide Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 mg Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 126 122 123 127 130 127 123 128 124 126 127 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.30  (0.058) -0.75  (0.059) -0.80  (0.059) -0.50  (0.058) -1.01  (0.058) -1.04  (0.058) -0.57  (0.059) -1.05  (0.058) -1.02  (0.059) -0.76  (0.058) -1.11  (0.058) -1.20  (0.058)
6.Secondary Outcome
Title Change From Baseline to Week 12 in HbA1c
Hide Description

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 mg Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 126 122 123 127 130 127 123 128 124 126 127 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.28  (0.067) -0.84  (0.069) -0.92  (0.068) -0.65  (0.067) -1.24  (0.066) -1.26  (0.067) -0.77  (0.068) -1.29  (0.067) -1.33  (0.068) -1.02  (0.067) -1.34  (0.067) -1.53  (0.067)
7.Secondary Outcome
Title Change From Baseline to Week 16 in HbA1c
Hide Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.
Time Frame Baseline and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward (LOCF) imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 mg Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 126 122 123 127 130 127 123 128 124 126 127 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.27  (0.071) -0.82  (0.072) -1.03  (0.072) -0.74  (0.071) -1.36  (0.070) -1.36  (0.071) -0.91  (0.072) -1.42  (0.071) -1.45  (0.072) -1.12  (0.071) -1.53  (0.071) -1.66  (0.071)
8.Secondary Outcome
Title Change From Baseline to Week 20 in HbA1c
Hide Description

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Time Frame Baseline and Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 mg + Pioglitazone 30 mg Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 mg Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 126 122 123 127 130 127 123 128 124 126 127 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.24  (0.074) -0.75  (0.075) -0.99  (0.075) -0.75  (0.074) -1.39  (0.073) -1.37  (0.074) -0.90  (0.075) -1.43  (0.074) -1.49  (0.075) -1.10  (0.074) -1.57  (0.074) -1.66  (0.074)
9.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis)
Hide Description

The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Time Frame Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 1 (n=358, 355, 354) -4.1  (1.56) -22.6  (1.57) -23.1  (1.57)
Week 2 (n=379, 383, 381) -11.3  (1.62) -30.3  (1.61) -31.6  (1.62)
Week 4 (n=381, 386, 383) -19.9  (1.67) -36.8  (1.66) -39.8  (1.67)
Week 8 (n=381, 386, 383) -27.3  (1.77) -42.3  (1.76) -45.2  (1.77)
Week 12 (n=381, 386, 383) -30.3  (1.84) -45.0  (1.83) -47.6  (1.83)
Week 16 (n=381, 386, 383) -27.9  (1.86) -43.7  (1.85) -45.4  (1.86)
Week 20 (n=381, 386, 383) -28.1  (2.00) -43.6  (1.99) -45.0  (1.99)
Week 26 (n=381, 386, 383) -28.3  (2.03) -45.2  (2.02) -44.2  (2.03)
10.Secondary Outcome
Title Change From Baseline to Week 1 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 123 114 117 120 121 123 117 119 118 121 115 113
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.8  (2.67) -14.5  (2.77) -18.6  (2.73) -6.1  (2.70) -21.3  (2.69) -20.9  (2.66) 0.4  (2.73) -23.2  (2.71) -23.2  (2.72) -6.7  (2.69) -23.2  (2.76) -25.0  (2.78)
11.Secondary Outcome
Title Change From Baseline to Week 2 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 120 125 127 127 129 124 128 126 128 128 126
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
4.8  (2.78) -21.9  (2.88) -18.9  (2.82) -10.4  (2.80) -30.1  (2.80) -31.7  (2.78) -4.3  (2.83) -30.0  (2.79) -31.3  (2.81) -19.3  (2.79) -30.8  (2.79) -31.7  (2.81)
12.Secondary Outcome
Title Change From Baseline to Week 4 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 125 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
3.8  (2.87) -20.4  (2.95) -22.8  (2.92) -20.2  (2.90) -35.3  (2.87) -37.3  (2.86) -13.4  (2.92) -37.4  (2.88) -36.0  (2.91) -26.1  (2.87) -37.8  (2.89) -46.2  (2.89)
13.Secondary Outcome
Title Change From Baseline to Week 8 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
5.7  (3.05) -19.5  (3.14) -19.3  (3.09) -22.2  (3.07) -42.3  (3.05) -39.3  (3.04) -24.0  (3.10) -40.5  (3.05) -44.1  (3.08) -35.6  (3.05) -44.0  (3.06) -52.3  (3.07)
14.Secondary Outcome
Title Change From Baseline to Week 12 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
3.4  (3.16) -19.3  (3.25) -23.3  (3.19) -23.0  (3.18) -42.9  (3.16) -42.5  (3.14) -26.6  (3.21) -42.8  (3.16) -49.0  (3.19) -41.3  (3.16) -49.2  (3.17) -51.4  (3.18)
15.Secondary Outcome
Title Change From Baseline to Week 16 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.4  (3.20) -16.2  (3.29) -22.6  (3.24) -21.2  (3.22) -41.6  (3.20) -39.1  (3.19) -26.3  (3.25) -41.5  (3.20) -43.4  (3.24) -36.3  (3.20) -47.9  (3.21) -53.8  (3.22)
16.Secondary Outcome
Title Change From Baseline to Week 20 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
6.7  (3.43) -8.7  (3.53) -23.5  (3.48) -22.4  (3.46) -43.0  (3.43) -39.3  (3.42) -26.3  (3.49) -41.1  (3.44) -43.1  (3.47) -35.7  (3.43) -46.8  (3.45) -52.4  (3.46)
17.Secondary Outcome
Title Change From Baseline to Week 26 in Fasting Plasma Glucose
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 126 129 128 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
6.5  (3.50) -13.2  (3.59) -18.6  (3.54) -23.6  (3.52) -42.0  (3.50) -38.0  (3.48) -28.8  (3.55) -42.2  (3.50) -41.7  (3.54) -32.4  (3.49) -51.3  (3.51) -52.7  (3.52)
18.Secondary Outcome
Title Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)
Hide Description

Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame From Week 1 to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 381 386 384
Measure Type: Number
Unit of Measure: percentage of participants
39.4 24.6 22.1
19.Secondary Outcome
Title Percentage of Participants With Marked Hyperglycemia
Hide Description Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
Time Frame From Week 1 to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 122 126 127 129 130 125 129 127 129 128 127
Measure Type: Number
Unit of Measure: percentage of participants
60.5 42.6 39.7 37.8 27.1 22.3 39.2 26.4 23.6 41.1 20.3 20.5
20.Secondary Outcome
Title Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)
Hide Description

Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:

  1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;
  2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;
  3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;
  4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time Frame From Week 1 to Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set including patients with at least 1 postbaseline visit. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 376 382 377
Measure Type: Number
Unit of Measure: percentage of participants
11.4 3.9 3.4
21.Secondary Outcome
Title Percentage of Participants Meeting Rescue Criteria
Hide Description

Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:

  1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;
  2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;
  3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;
  4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.
Time Frame From Week 1 to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set including patients with at least 1 postbaseline visit.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 125 124 125 127 129 129 123 126 123 126 127 125
Measure Type: Number
Unit of Measure: percentage of participants
32.8 14.5 12.8 10.2 4.7 3.9 15.4 4.8 4.9 8.7 2.4 1.6
22.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
12.4 27.9 29.2
23.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
0.8 8.6 12.4 6.2 21.5 24.6 11.6 30.0 30.0 19.4 32.3 33.1
24.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
30.5 54.6 55.9
25.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 7%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
6.2 22.7 27.1 25.6 49.2 54.6 29.5 53.1 53.1 36.4 61.5 60.0
26.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
54.8 77.4 74.1
27.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
24.8 38.3 55.0 51.9 77.7 71.5 55.8 73.8 72.3 56.6 80.8 78.5
28.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
67.2 85.6 83.3
29.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
31.8 57.8 66.7 61.2 86.2 79.2 68.2 86.9 83.8 72.1 83.8 86.9
30.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
45.7 71.8 69.5
31.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
16.3 33.6 47.3 36.4 69.2 66.9 46.5 73.1 69.2 54.3 73.1 72.3
32.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
27.6 45.9 50.3
33.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
5.4 15.6 28.7 21.7 41.5 46.2 27.1 45.4 46.2 34.1 50.8 58.5
34.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)
Hide Description

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Measure Type: Number
Unit of Measure: percentage of participants
11.1 25.4 27.7
35.Secondary Outcome
Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%
Hide Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 129 128 129 129 130 130 129 130 130 129 130 130
Measure Type: Number
Unit of Measure: percentage of participants
1.6 7.8 11.6 7.0 23.1 21.5 9.3 22.3 26.2 17.1 30.8 35.4
36.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis)
Hide Description

Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.

Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone
Hide Arm/Group Description:
Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).
Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).
Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).
Overall Number of Participants Analyzed 387 390 390
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
Week 4 (n=328, 319, 327) -6.2  (0.81) -10.3  (0.82) -10.1  (0.81)
Week 8 (n=357, 347, 358) -7.2  (0.87) -11.3  (0.88) -11.3  (0.87)
Week 12 (n=357, 347, 358) -8.2  (0.91) -11.6  (0.93) -11.6  (0.91)
Week 16 (n=358, 348, 358) -7.2  (0.92) -12.2  (0.94) -11.3  (0.92)
Week 20 (n=358, 349, 359) -6.6  (1.08) -10.4  (1.09) -10.7  (1.08)
Week 26 (n=358, 349, 359) -5.3  (1.09) -10.6  (1.11) -9.5  (1.09)
37.Secondary Outcome
Title Change From Baseline to Week 4 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 116 111 109 107 109 109 110 105 114 111 105 104
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-0.1  (1.36) -4.7  (1.39) -2.3  (1.41) -4.8  (1.42) -9.9  (1.41) -8.9  (1.41) -6.7  (1.40) -9.6  (1.43) -9.5  (1.37) -7.2  (1.39) -11.3  (1.43) -11.7  (1.44)
38.Secondary Outcome
Title Change From Baseline to Week 8 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 122 120 123 121 119 120 116 113 119 120 115 119
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
0.7  (1.48) 0.2  (1.50) -2.6  (1.48) -3.8  (1.49) -11.1  (1.50) -10.7  (1.50) -8.8  (1.52) -11.8  (1.54) -9.4  (1.50) -9.0  (1.50) -11.0  (1.53) -13.8  (1.50)
39.Secondary Outcome
Title Change From Baseline to Week 12 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 122 120 123 121 119 120 116 113 119 120 115 119
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-1.0  (1.56) -0.7  (1.57) -2.3  (1.56) -5.3  (1.57) -10.1  (1.58) -8.8  (1.58) -11.2  (1.60) -12.1  (1.63) -12.7  (1.58) -8.1  (1.58) -12.7  (1.61) -13.2  (1.58)
40.Secondary Outcome
Title Change From Baseline to Week 16 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 122 120 123 121 120 120 117 113 119 120 115 119
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-3.0  (1.58) 0.0  (1.60) -2.3  (1.58) -3.7  (1.59) -11.0  (1.60) -8.4  (1.60) -10.0  (1.62) -12.6  (1.65) -11.2  (1.60) -8.0  (1.60) -13.0  (1.63) -14.4  (1.60)
41.Secondary Outcome
Title Change From Baseline to Week 20 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 122 120 123 121 121 121 117 113 119 120 115 119
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-0.9  (1.85) 1.5  (1.86) -3.0  (1.84) -3.4  (1.86) -11.2  (1.86) -8.7  (1.86) -9.3  (1.89) -10.0  (1.92) -10.7  (1.87) -7.1  (1.86) -10.2  (1.90) -12.5  (1.87)
42.Secondary Outcome
Title Change From Baseline to Week 26 in Fasting Proinsulin
Hide Description Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.
Time Frame Baseline and Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Placebo Alogliptin 12.5 + Placebo Alogliptin 25 + Placebo Placebo + Pioglitazone 15 Alogliptin 12.5 + Pioglitazone 15 Alogliptin 25 + Pioglitazone 15 Placebo + Pioglitazone 30 Alogliptin 12.5 + Pioglitazone 30 Alogliptin 25 + Pioglitazone 30 Placebo + Pioglitazone 45 Alogliptin 12.5 + Pioglitazone 45 Alogliptin 25 + Pioglitazone 45
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Number of Participants Analyzed 122 120 123 121 121 121 117 113 119 120 115 119
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
1.2  (1.87) 0.7  (1.88) -3.3  (1.86) -3.5  (1.88) -10.9  (1.88) -7.2  (1.88) -8.4  (1.91) -8.9  (1.95) -8.8  (1.89) -4.1  (1.89) -12.1  (1.93) -12.6  (1.89)
43.Secondary Outcome
Title Change From Baseline in Insulin Over Time (Grouped Analysis)
Hide Description The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.
Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.
Arm/Group Title Pioglitazone Alone Alogliptin 12.5 + Pioglitazone Alogliptin 25 + Pioglitazone