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

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ClinicalTrials.gov Identifier: NCT00286442
Recruitment Status : Completed
First Posted : February 3, 2006
Results First Posted : August 25, 2011
Last Update Posted : February 3, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Drug: Alogliptin and metformin
Drug: Metformin
Enrollment 527
Recruitment Details Participants enrolled at 115 investigative sites in Australia, Brazil, Chile, Germany, Guatemala, Hungary, India, Mexico, New Zealand, The Netherlands, Poland, South Africa, Spain, and the United States from 10 March 2006 to 12 June 2007.
Pre-assignment Details Participants with a historical diagnosis of type 2 diabetes mellitus who were inadequately controlled while receiving a stable dose of metformin monotherapy were enrolled in one of 3, once-daily (QD) treatment groups.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Period Title: Overall Study
Started 213 210 104
Completed 176 165 72
Not Completed 37 45 32
Reason Not Completed
Hyperglycemic Rescue             19             17             25
Adverse Event             7             6             1
Protocol Violation             2             4             2
Lost to Follow-up             5             2             1
Physician Decision             1             1             1
Administrative Error             1             1             0
Withdrawal by Subject             2             14             2
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo Total
Hide Arm/Group Description Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks. Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks. Total of all reporting groups
Overall Number of Baseline Participants 213 210 104 527
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 213 participants 210 participants 104 participants 527 participants
<65 years 173 179 83 435
≥65 years 40 31 21 92
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 213 participants 210 participants 104 participants 527 participants
Female
112
  52.6%
96
  45.7%
54
  51.9%
262
  49.7%
Male
101
  47.4%
114
  54.3%
50
  48.1%
265
  50.3%
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.
Hide Description The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 26.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 203 103
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.61  (0.053) -0.59  (0.054) -0.10  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments Null Hypothesis: No difference between treatment and placebo arms in change from baseline in glycosylated hemoglobin at wk 26. Sample size calculated based on normally distributed means. For comparison of either dose vs. placebo (2-sample t-test), study sample size >=500 participants had 95% power to detect a treatment difference as small as 0.4% in the supportive per protocol analysis set assuming SD=0.8%, 2-sided >0.05 significance level and >=80% of participants meeting per protocol criteria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
Method ANCOVA
Comments Analysis of covariance (ANCOVA) with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.68 to -0.32
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments Null Hypothesis: No difference between treatment and placebo arms in change from baseline in glycosylated hemoglobin at week 26. Sample size calculated based on normally distributed means. For comparison of either dose vs. placebo (2-sample t-test), study sample size >=500 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming SD=0.8%, 2-sided test at 0.05 significance level and >=80% of participants meeting per protocol criteria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.67 to -0.30
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
2.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 4).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 188 187 91
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.36  (0.031) -0.40  (0.031) -0.10  (0.044)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.37 to -0.16
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.40 to -0.19
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
3.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 8).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 8.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 201 103
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.59  (0.041) -0.59  (0.042) -0.21  (0.058)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.52 to -0.24
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.52 to -0.24
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
4.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 12).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 12.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 203 103
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.66  (0.047) -0.66  (0.048) -0.16  (0.067)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.66 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.66 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
5.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 16).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 16.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 203 103
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.66  (0.050) -0.64  (0.051) -0.13  (0.072)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-0.70 to -0.36
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.69 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
6.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 20).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an HbA1c measurement at baseline and at Week 20.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 203 103
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.63  (0.051) -0.63  (0.052) -0.12  (0.073)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.69 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA on change from baseline with treatment and geographic region as class variables and baseline metformin dose and baseline HbA1c as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.69 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
7.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 1).
Hide Description The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 1.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 1.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 193 186 98
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-14.3  (2.05) -12.5  (2.09) -0.6  (2.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates. Missing data imputed with LOCF.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.7
Confidence Interval (2-Sided) 95%
-20.7 to -6.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the metformin arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates. Missing data imputed with LOCF.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.9
Confidence Interval (2-Sided) 95%
-18.9 to -4.9
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the metformin arm.
8.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 2).
Hide Description The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 2.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 2.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 208 199 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-17.4  (2.11) -17.6  (2.16) -0.7  (2.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates. Missing data imputed with LOCF.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.7
Confidence Interval (2-Sided) 95%
-23.9 to -9.5
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates. Missing data imputed with LOCF.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.8
Confidence Interval (2-Sided) 95%
-24.1 to -9.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
9.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 4).
Hide Description The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 2. Missing data imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-18.4  (1.98) -18.1  (2.01) -0.6  (2.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.8
Confidence Interval (2-Sided) 95%
-24.6 to -11.0
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.5
Confidence Interval (2-Sided) 95%
-24.3 to -10.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
10.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 8).
Hide Description The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-19.6  (2.30) -17.2  (2.34) 0.4  (3.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.1
Confidence Interval (2-Sided) 95%
-28.0 to -12.2
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.6
Confidence Interval (2-Sided) 95%
-25.6 to -9.7
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
11.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 12).
Hide Description The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-16.9  (2.44) -16.8  (2.47) 0.3  (3.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.2
Confidence Interval (2-Sided) 95%
-25.6 to -8.9
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.0
Confidence Interval (2-Sided) 95%
-25.4 to -8.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
12.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 16).
Hide Description The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-17.8  (2.43) -15.4  (2.46) 1.3  (3.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -19.1
Confidence Interval (2-Sided) 95%
-27.4 to -10.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.7
Confidence Interval (2-Sided) 95%
-25.0 to -8.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
13.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 20).
Hide Description The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-18.1  (2.53) -15.6  (2.57) -0.1  (3.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.1
Confidence Interval (2-Sided) 95%
-26.7 to -9.4
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.5
Confidence Interval (2-Sided) 95%
-24.2 to -6.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
14.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 26).
Hide Description The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 204 104
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-18.7  (2.49) -17.4  (2.53) 0.0  (3.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.7
Confidence Interval (2-Sided) 95%
-27.3 to -10.2
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.4
Confidence Interval (2-Sided) 95%
-25.9 to -8.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
15.Secondary Outcome
Title Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).
Hide Description The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.
Time Frame 26 Weeks.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 fasting plasma glucose measurement after baseline.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 206 104
Measure Type: Number
Unit of Measure: participants
61 65 53
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments no multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin dose and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.372
Confidence Interval (2-Sided) 95%
0.213 to 0.650
Estimation Comments Odd's Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin dose and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.405
Confidence Interval (2-Sided) 95%
0.231 to 0.708
Estimation Comments Odd's Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
16.Secondary Outcome
Title Number of Participants Requiring Rescue.
Hide Description The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.
Time Frame 26 Weeks.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 study visit after baseline.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 211 207 104
Measure Type: Number
Unit of Measure: participants
19 17 25
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments no multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin dose and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.302
Confidence Interval (2-Sided) 95%
0.143 to 0.635
Estimation Comments Odd's Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
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 Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin dose and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.236
Confidence Interval (2-Sided) 95%
0.109 to 0.510
Estimation Comments Odd's Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
17.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 4).
Hide Description The change between the value of fasting proinsulin collected at week 4 and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a fasting plasma glucose measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 178 174 90
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-1.9  (1.76) -5.0  (1.77) -0.5  (2.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.634
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-7.4 to 4.5
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.136
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-10.5 to 1.4
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
18.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 8).
Hide Description The change between the value of fasting proinsulin collected at week 8 and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 201 189 100
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-2.9  (1.30) -5.0  (1.34) -0.4  (1.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.274
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-6.9 to 2.0
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments No multiplicity adjustments.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-9.1 to -0.1
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
19.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 12).
Hide Description The change between the value of fasting proinsulin collected at week 12 and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 201 191 100
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-2.6  (1.76) -2.7  (1.8) -1.3  (2.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.655
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-7.4 to 4.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.645
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline FPG as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-7.4 to 4.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
20.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 16).
Hide Description The change between the value of fasting proinsulin collected at week 16 and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 201 191 100
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-1.4  (1.60) -2.7  (1.64) -0.5  (2.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.748
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-6.3 to 4.6
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.432
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-7.7 to 3.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
21.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 20).
Hide Description The change between the value of fasting proinsulin collected at week 20 and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a proinsulin measurement at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 201 191 100
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-4.2  (1.62) -1.1  (1.66) -2.0  (2.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-7.8 to 3.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.746
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-4.6 to 6.5
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
22.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin (Week 26).
Hide Description The change between the value of fasting proinsulin collected at week 26 or final visit and fasting proinsulin collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a PROINSULIN measurement at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 201 191 100
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
-2.1  (1.80) -1.6  (1.84) -3.2  (2.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.727
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-5.0 to 7.2
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.6
Comments No multiplicity adjustments
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.601
Confidence Interval (2-Sided) 95%
-4.5 to 7.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
23.Secondary Outcome
Title Change From Baseline in Insulin (Week 4).
Hide Description The change between the value of insulin collected at week 4 and insulin collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had an insulin measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 177 170 89
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
1.11  (0.684) 0.52  (0.695) -1.07  (0.965)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
-0.15 to 4.52
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.180
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.60
Confidence Interval (2-Sided) 95%
-0.74 to 3.93
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
24.Secondary Outcome
Title Change From Baseline in Insulin (Week 8).
Hide Description The change between the value of insulin collected at week 8 and insulin collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 186 99
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
2.50  (1.416) 0.18  (1.466) 2.68  (2.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.944
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-5.02 to 4.68
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.316
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-7.40 to 2.40
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
25.Secondary Outcome
Title Change From Baseline in Insulin (Week 12).
Hide Description The change between the value of insulin collected at week 12 and insulin collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
1.6  (1.488) 0.46  (1.532) 1.92  (2.118)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-5.42 to 4.77
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.45
Confidence Interval (2-Sided) 95%
-6.59 to 3.68
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
26.Secondary Outcome
Title Change From Baseline in Insulin (Week 16).
Hide Description The change between the value of insulin collected at week 16 and insulin collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
1.27  (0.964) 1.53  (0.993) 0.64  (1.372)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.708
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-2.67 to 3.93
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.601
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
-2.44 to 4.21
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
27.Secondary Outcome
Title Change From Baseline in Insulin (Week 20).
Hide Description The change between the value of insulin collected at week 20 and insulin collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
0.91  (0.760) 0.86  (0.782) -0.21  (1.081)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.398
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-1.48 to 3.72
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.425
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
-1.56 to 3.69
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
28.Secondary Outcome
Title Change From Baseline in Insulin (Week 26).
Hide Description The change between the value of insulin collected at week 26 and insulin collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had a Insulin measurement at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
0.63  (0.690) -0.01  (0.710) -2.23  (0.981)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.87
Confidence Interval (2-Sided) 95%
0.50 to 5.23
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline insulin as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.22
Confidence Interval (2-Sided) 95%
-0.15 to 4.60
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
29.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 4).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 4 and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 177 170 89
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.045  (0.0082) -0.056  (0.0083) -0.008  (0.0115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.036
Confidence Interval (2-Sided) 95%
-0.064 to -0.009
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.047
Confidence Interval (2-Sided) 95%
-0.075 to -0.019
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
30.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 8).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 8 and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF.
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 186 99
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.055  (0.0073) -0.046  (0.0075) -0.009  (0.0103)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.045
Confidence Interval (2-Sided) 95%
-0.070 to -0.021
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.037
Confidence Interval (2-Sided) 95%
-0.062 to -0.012
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
31.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 12).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 12 and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.044  (0.0083) -0.042  (0.0085) -0.005  (0.0118)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.039
Confidence Interval (2-Sided) 95%
-0.068 to -0.011
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.037
Confidence Interval (2-Sided) 95%
-0.066 to -0.008
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm
32.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 16).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 16 and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.051  (0.0082) -0.043  (0.0085) 0.001  (0.0117)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.052
Confidence Interval (2-Sided) 95%
-0.080 to -0.024
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.044
Confidence Interval (2-Sided) 95%
-0.072 to -0.015
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
33.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 20).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 20 and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.53  (0.0150) -0.011  (0.0155) -0.007  (0.0213)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.046
Confidence Interval (2-Sided) 95%
-0.097 to 0.005
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.860
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.005
Confidence Interval (2-Sided) 95%
-0.056 to 0.047
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
34.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio (Week 26).
Hide Description The change between the ratio value of proinsulin and insulin collected at week 26 or final visit and the ratio value of proinsulin and insulin collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had insulin and proinsulin measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 200 188 99
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.049  (0.0154) 0.000  (0.0159) 0.004  (0.0219)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.053
Confidence Interval (2-Sided) 95%
-0.106 to -0.001
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.889
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline proinsulin/insulin ratio as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.004
Confidence Interval (2-Sided) 95%
-0.057 to 0.050
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
35.Secondary Outcome
Title Change From Baseline in C-peptide (Week 4).
Hide Description The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.
Time Frame Baseline and Week 4.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 186 184 92
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.222  (0.0893) 0.190  (0.0897) -0.114  (0.1273)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.336
Confidence Interval (2-Sided) 95%
0.030 to 0.642
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.304
Confidence Interval (2-Sided) 95%
-0.002 to 0.611
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
36.Secondary Outcome
Title Change From Baseline in C-peptide (Week 8).
Hide Description The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.
Time Frame Baseline and Week 8.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 200 103
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.215  (0.0864) 0.238  (0.0884) 0.127  (0.1236)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.563
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.088
Confidence Interval (2-Sided) 95%
-0.209 to 0.384
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.111
Confidence Interval (2-Sided) 95%
-0.188 to 0.410
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
37.Secondary Outcome
Title Change From Baseline in C-peptide (Week 12).
Hide Description The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.
Time Frame Baseline and Week 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 202 103
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.154  (0.0915) 0.246  (0.0932) -0.033  (0.1309)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.243
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.187
Confidence Interval (2-Sided) 95%
-0.127 to 0.501
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.279
Confidence Interval (2-Sided) 95%
-0.037 to 0.595
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
38.Secondary Outcome
Title Change From Baseline in C-peptide (Week 16).
Hide Description The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 202 103
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.138  (0.0894) 0.250  (0.0910) -0.018  (0.1280)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.321
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.155
Confidence Interval (2-Sided) 95%
-0.152 to 0.463
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.089
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.268
Confidence Interval (2-Sided) 95%
-0.041 to 0.577
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
39.Secondary Outcome
Title Change From Baseline in C-peptide (Week 20).
Hide Description The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.
Time Frame Baseline and Week 20.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 202 103
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.007  (0.0803) 0.054  (0.0818) -0.137  (0.1149)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.305
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.144
Confidence Interval (2-Sided) 95%
-0.132 to 0.420
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments No multiplicity adjustments.
Method ANCOVA
Comments Treatment and geographic region as class variables; baseline metformin dose and baseline C-peptide as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.191
Confidence Interval (2-Sided) 95%
-0.086 to 0.468
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
40.Secondary Outcome
Title Change From Baseline in C-peptide (Week 26).
Hide Description The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.
Time Frame Baseline and Week 26.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug (Full Analysis Set), and who had C-peptide measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 12.5 mg QD Alogliptin 25 mg QD Placebo
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.
Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Overall Number of Participants Analyzed 210 202 103
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-0.083  (0.0833) -0.214  (0.0848) -0.476  (0.1192)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other