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Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus (ENDURE)

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ClinicalTrials.gov Identifier: NCT00856284
Recruitment Status : Completed
First Posted : March 5, 2009
Results First Posted : December 3, 2013
Last Update Posted : December 3, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Alogliptin
Drug: Metformin
Drug: Glipizide
Enrollment 2639

Recruitment Details Participants took part in the study at 310 study sites worldwide from 05 March 2009 to 17 October 2012.
Pre-assignment Details Participants with type 2 diabetes mellitus experiencing inadequate glycemic control while on metformin therapy were enrolled equally in 1 of 3 treatment groups: alogliptin 12.5 mg once daily (QD), alogliptin 25 mg QD, and glipizide 5 mg QD.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Period Title: Overall Study
Started 880 885 874
Received Study Drug 873 878 869
Completed 472 493 427
Not Completed 408 392 447
Reason Not Completed
Hyperglycemic rescue             231             201             235
Adverse Event             60             74             82
Major protocol deviation             24             16             15
Lost to Follow-up             20             22             28
Voluntary withdrawal             48             52             62
Pregnancy             1             2             0
Investigator discretion             9             8             10
Other             15             17             14
Randomized in error             0             0             1
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide Total
Hide Arm/Group Description Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals. Total of all reporting groups
Overall Number of Baseline Participants 880 885 874 2639
Hide Baseline Analysis Population Description
The Randomized Set included all enrolled subjects who were subsequently randomized.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
55.2  (9.60) 55.5  (9.81) 55.4  (9.60) 55.4  (9.67)
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
<65 years 734 710 723 2167
≥65 years 146 175 151 472
≥75 years 13 17 15 45
[1]
Measure Description: Categories ≥65 years and ≥75 years are not mutually exclusive. Participants ≥75 years are counted in both categories.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
Female
461
  52.4%
433
  48.9%
433
  49.5%
1327
  50.3%
Male
419
  47.6%
452
  51.1%
441
  50.5%
1312
  49.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
American Indian or Alaska Native 40 42 36 118
Asian 191 207 203 601
Black or African American 74 66 81 221
Native Hawaiian or Other Pacific Islander 7 1 4 12
White 557 555 533 1645
Multiracial 11 14 17 42
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
Hispanic or Latino 192 204 192 588
Not Hispanic or Latino 688 681 682 2051
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
31.27  (5.417) 31.27  (5.341) 31.11  (5.320) 31.22  (5.358)
[1]
Measure Description: BMI data available for 879, 885 and 872 participants in each treatment arm, respectively.
Glycosylated hemoglobin (HbA1c)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
7.59  (0.599) 7.61  (0.606) 7.60  (0.617) 7.60  (0.607)
[1]
Measure Description: Mean HbA1c data includes 877, 883 and 870 participants in each treatment arm, respectively.
Baseline HbA1c Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
<8.0% 615 620 613 1848
≥8.0% 265 265 261 791
Diabetes duration   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
5.65  (5.324) 5.42  (4.730) 5.48  (4.884) 5.52  (4.985)
[1]
Measure Description: Diabetes duration data available for 880, 884 and 874 participants in each treatment arm, respectively.
Metformin dose  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
1825.2  (405.59) 1837.2  (373.06) 1823.4  (390.63) 1828.6  (389.85)
Glomerular filtration rate   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
MDRD 83.04  (16.586) 82.35  (16.199) 82.28  (16.994) 82.56  (16.591)
Cockcroft-Gault 109.3  (33.40) 109.3  (32.85) 108.0  (32.64) 108.9  (32.96)
[1]
Measure Description: Glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease (MDRD) formula and the Cockcroft-Gault formula. Data include 877, 883 and 870 participants in each treatment arm, respectively.
Smoking history  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 880 participants 885 participants 874 participants 2639 participants
Never smoked 543 586 578 1707
Current smoker 135 122 111 368
Ex-smoker 202 177 185 564
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
Hide Description The change from Baseline to Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol set included all randomized patients who took at least 1 dose of double-blind study drug, with a Baseline assessment and at least 1 post-baseline assessment for that variable and who had no major protocol violations. Last observation carried forward (LOCF) was used.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 371 382 336
Least Squares Mean (Standard Error)
Unit of Measure: percentage glycosylated hemoglobin
-0.81  (0.027) -0.76  (0.027) -0.73  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin + Alogliptin 25 mg, Metformin + Glipizide
Comments The null hypotheses were tested in a fixed order at the 1-sided 0.0125 significance level at Weeks 52 and 104, independently: H01: Alogliptin 25 mg was inferior in HbA1c change from Baseline vs glipizide. H02: Alogliptin 12.5 mg was inferior vs glipizide. H03: Alogliptin 25 mg was not superior vs glipizide. H04: Alogliptin 12.5 mg was not superior vs glipizide. Each subsequent null hypothesis was tested only if all previously tested null hypotheses were rejected with respect to Weeks 52 and 104.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.03
Confidence Interval (1-Sided) 98.75%
0.059
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin + Alogliptin 12.5 mg, Metformin + Glipizide
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.09
Confidence Interval (1-Sided) 98.75%
0.003
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104
Hide Description The change from Baseline to Week 104 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Week 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol set included all randomized patients who took at least 1 dose of double-blind study drug, with a Baseline assessment and at least 1 post-baseline assessment for that variable and who had no major protocol violations. Last observation carried forward was used (LOCF).
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 371 382 336
Least Squares Mean (Standard Error)
Unit of Measure: percentage glycosylated hemoglobin
-0.68  (0.037) -0.72  (0.037) -0.59  (0.039)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin + Alogliptin 25 mg, Metformin + Glipizide
Comments The null hypotheses were tested in a fixed order at the 1-sided 0.0125 significance level at Weeks 52 and 104, independently: H01: Alogliptin 25 mg was inferior in HbA1c change from Baseline vs glipizide. H02: Alogliptin 12.5 mg was inferior vs glipizide. H03: Alogliptin 25 mg was not superior vs glipizide. H04: Alogliptin 12.5 mg was not superior vs glipizide. Each subsequent null hypothesis was tested only if all previously tested null hypotheses were rejected with respect to Weeks 52 and 104.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.13
Confidence Interval (1-Sided) 98.75%
-0.006
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin + Alogliptin 12.5 mg, Metformin + Glipizide
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.09
Confidence Interval (1-Sided) 98.75%
0.035
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin at Other Time Points
Hide Description The change from Baseline over time in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set; LOCF was used.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 371 382 336
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
Week 4 (n=341, 354, 318) -0.37  (0.020) -0.40  (0.020) -0.41  (0.021)
Week 8 (n=370, 382, 336) -0.56  (0.024) -0.60  (0.024) -0.66  (0.025)
Week 12 (n=371, 382, 336) -0.69  (0.025) -0.71  (0.025) -0.78  (0.026)
Week 16 (n=371, 382, 336) -0.74  (0.026) -0.76  (0.025) -0.78  (0.027)
Week 20 (n=371, 382, 336) -0.76  (0.026) -0.78  (0.025) -0.79  (0.027)
Week 26 (n=371, 382, 336) -0.80  (0.027) -0.79  (0.026) -0.80  (0.028)
Week 39 (n=371, 382, 336) -0.81  (0.026) -0.81  (0.025) -0.74  (0.027)
Week 65 (n=371, 382, 336) -0.81  (0.029) -0.83  (0.028) -0.76  (0.030)
Week 78 (n=371, 382, 336) -0.82  (0.030) -0.80  (0.030) -0.73  (0.032)
Week 91 (n=371, 382, 336) -0.76  (0.033) -0.77  (0.033) -0.68  (0.035)
4.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose Over Time
Hide Description The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline FPG and Baseline metformin dose as covariates.
Time Frame Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, which included all randomized patients who received at least 1 dose of double-blind study drug who had a Baseline assessment and at least 1 post-baseline assessment for FPG. LOCF was used.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 867 867 859
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 2 (n=781, 803, 777) -10.2  (0.89) -11.4  (0.87) -7.7  (0.89)
Week 4 (n=863, 865, 855) -10.6  (0.85) -11.6  (0.85) -10.2  (0.85)
Week 8 (n=867, 867, 859) -9.2  (0.91) -11.6  (0.91) -9.3  (0.92)
Week 12 (n=867, 867, 859) -10.7  (0.94) -11.2  (0.94) -9.4  (0.95)
Week 16 (n=867, 867, 859) -8.6  (0.98) -9.9  (0.98) -7.1  (0.98)
Week 20 (n=867, 867, 859) -7.6  (1.02) -10.1  (1.02) -5.5  (1.02)
Week 26 (n=867, 867, 859) -7.5  (1.06) -10.1  (1.06) -4.3  (1.06)
Week 39 (n=867, 867, 859) -6.9  (1.14) -8.4  (1.14) -0.6  (1.15)
Week 52 (n=867, 867, 859) -5.0  (1.22) -7.0  (1.22) 0.9  (1.23)
Week 65 (n=867, 867, 859) -3.4  (1.21) -5.9  (1.21) 1.4  (1.21)
Week 78 (n=867, 867, 859) -2.8  (1.47) -5.1  (1.47) 5.1  (1.48)
Week 91 (n=867, 867, 859) -0.9  (1.27) -3.4  (1.27) 4.9  (1.28)
Week 104 (n=867, 867, 859) -0.9  (1.28) -3.2  (1.28) 5.4  (1.29)
5.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
Hide Description The percentage of participants with HbA1c less than or equal to 6.5% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
Time Frame Weeks 26, 52, 78, and 104.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 873 878 869
Measure Type: Number
Unit of Measure: percentage of participants
Week 26 25.6 26.2 24.8
Week 52 24.5 24.8 20.8
Week 78 24.2 26.4 21.8
Week 104 23.5 24.1 19.0
6.Secondary Outcome
Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
Hide Description Percentage of participants with HbA1c ≤ 7.0% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
Time Frame Weeks 26, 52, 78, and 104.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 873 878 869
Measure Type: Number
Unit of Measure: percentage of participants
Week 26 56.4 59.2 56.1
Week 52 51.7 55.5 47.4
Week 78 48.8 52.4 46.6
Week 104 45.6 48.5 42.8
7.Secondary Outcome
Title Change From Baseline in Body Weight Over Time
Hide Description LS Means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and Baseline weight and Baseline metformin dose as covariates.
Time Frame Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, LOCF was used.
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description:
Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Overall Number of Participants Analyzed 867 868 861
Least Squares Mean (Standard Error)
Unit of Measure: kg
Week 12 -0.51  (0.076) -0.53  (0.076) 0.71  (0.077)
Week 26 -0.65  (0.101) -0.71  (0.101) 0.86  (0.101)
Week 39 -0.60  (0.109) -0.86  (0.109) 0.97  (0.110)
Week 52 -0.63  (0.117) -0.90  (0.117) 0.89  (0.117)
Week 65 -0.70  (0.122) -0.92  (0.122) 0.87  (0.123)
Week 78 -0.78  (0.124) -0.94  (0.124) 0.88  (0.125)
Week 91 -0.67  (0.127) -0.88  (0.127) 0.89  (0.127)
Week 104 -0.68  (0.127) -0.89  (0.127) 0.95  (0.127)
Time Frame Collection of adverse events commenced from the time the participant was first administered double-blind study medication until the end of the study and from spontaneous reporting for 30 days after the end of treatment (up to 108 weeks).
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Hide Arm/Group Description Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
All-Cause Mortality
Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   86/873 (9.85%)   97/878 (11.05%)   81/869 (9.32%) 
Blood and lymphatic system disorders       
Anaemia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Iron deficiency anaemia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Cardiac disorders       
Coronary artery disease  1  5/873 (0.57%)  3/878 (0.34%)  2/869 (0.23%) 
Angina unstable  1  1/873 (0.11%)  4/878 (0.46%)  4/869 (0.46%) 
Acute myocardial infarction  1  0/873 (0.00%)  1/878 (0.11%)  5/869 (0.58%) 
Atrial fibrillation  1  1/873 (0.11%)  3/878 (0.34%)  2/869 (0.23%) 
Atrial flutter  1  2/873 (0.23%)  2/878 (0.23%)  1/869 (0.12%) 
Cardiac failure  1  0/873 (0.00%)  3/878 (0.34%)  1/869 (0.12%) 
Cardiac failure congestive  1  2/873 (0.23%)  1/878 (0.11%)  1/869 (0.12%) 
Myocardial infarction  1  0/873 (0.00%)  1/878 (0.11%)  3/869 (0.35%) 
Angina pectoris  1  0/873 (0.00%)  2/878 (0.23%)  1/869 (0.12%) 
Myocardial ischaemia  1  1/873 (0.11%)  0/878 (0.00%)  2/869 (0.23%) 
Atrioventricular block complete  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Cardiomyopathy  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Silent myocardial infarction  1  0/873 (0.00%)  2/878 (0.23%)  0/869 (0.00%) 
Acute coronary syndrome  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Arteriosclerosis coronary artery  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Atrioventricular block  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Atrioventricular block second degree  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Bradycardia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Congestive cardiomyopathy  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Coronary artery occlusion  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Left ventricular failure  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Pericardial effusion  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Right ventricular failure  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Tachyarrhythmia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Ear and labyrinth disorders       
Acute vestibular syndrome  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Vertigo  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Vertigo positional  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Endocrine disorders       
Primary hyperaldosteronism  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Eye disorders       
Cataract  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Cataract nuclear  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Cataract subcapsular  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Iridocyclitis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Retinal detachment  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Vision blurred  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Gastrointestinal disorders       
Colitis  1  2/873 (0.23%)  2/878 (0.23%)  0/869 (0.00%) 
Abdominal pain  1  1/873 (0.11%)  0/878 (0.00%)  2/869 (0.23%) 
Inguinal hernia  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Nausea  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Pancreatitis acute  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Umbilical hernia  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Anal fistula  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Colitis ischaemic  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Diarrhoea  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Diverticulum  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Dyspepsia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Enterocolitis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Gastritis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Gastrointestinal haemorrhage  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Haematemesis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Haemorrhoids  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Intestinal ischaemia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Mallory-Weiss syndrome  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Pancreatitis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Umbilical hernia, obstructive  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Upper gastrointestinal haemorrhage  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Vomiting  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
General disorders       
Non-cardiac chest pain  1  3/873 (0.34%)  4/878 (0.46%)  3/869 (0.35%) 
Chest pain  1  0/873 (0.00%)  2/878 (0.23%)  0/869 (0.00%) 
Hernia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Sudden death  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Hepatobiliary disorders       
Cholecystitis  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Cholecystitis acute  1  0/873 (0.00%)  3/878 (0.34%)  0/869 (0.00%) 
Cholelithiasis  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Bile duct stone  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Drug-induced liver injury  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Infections and infestations       
Cellulitis  1  3/873 (0.34%)  1/878 (0.11%)  3/869 (0.35%) 
Pneumonia  1  1/873 (0.11%)  2/878 (0.23%)  2/869 (0.23%) 
Gastroenteritis  1  2/873 (0.23%)  2/878 (0.23%)  0/869 (0.00%) 
Dengue fever  1  1/873 (0.11%)  0/878 (0.00%)  2/869 (0.23%) 
Diverticulitis  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Hepatitis viral  1  1/873 (0.11%)  0/878 (0.00%)  2/869 (0.23%) 
Urinary tract infection  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Urosepsis  1  0/873 (0.00%)  1/878 (0.11%)  1/869 (0.12%) 
Abdominal abscess  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Abscess limb  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Acute sinusitis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Amoebiasis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Appendicitis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Bronchitis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Cystitis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Gangrene  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Gastroenteritis salmonella  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Lobar pneumonia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Malaria  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Osteomyelitis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Pneumocystis jiroveci pneumonia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Scrotal abscess  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Sepsis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Septic shock  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Staphylococcal infection  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  1/873 (0.11%)  2/878 (0.23%)  1/869 (0.12%) 
Fall  1  2/873 (0.23%)  0/878 (0.00%)  0/869 (0.00%) 
Joint injury  1  0/873 (0.00%)  0/878 (0.00%)  2/869 (0.23%) 
Road traffic accident  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Comminuted fracture  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Craniocerebral injury  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Facial bones fracture  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Femur fracture  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Incisional hernia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Joint dislocation  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Ligament rupture  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Lower limb fracture  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Patella fracture  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Peripheral nerve injury  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Tendon rupture  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Tibia fracture  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Diabetic ketoacidosis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Hypoglycaemia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  2/873 (0.23%)  3/878 (0.34%)  4/869 (0.46%) 
Musculoskeletal chest pain  1  1/873 (0.11%)  2/878 (0.23%)  1/869 (0.12%) 
Intervertebral disc protrusion  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Muscle haemorrhage  1  2/873 (0.23%)  0/878 (0.00%)  0/869 (0.00%) 
Spinal osteoarthritis  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Arthralgia  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Back pain  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Bursitis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Haemarthrosis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Myalgia intercostal  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Polymyositis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Spinal column stenosis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  2/873 (0.23%)  0/878 (0.00%)  1/869 (0.12%) 
Basal cell carcinoma  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Uterine leiomyoma  1  2/873 (0.23%)  0/878 (0.00%)  0/869 (0.00%) 
Adenocarcinoma  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Bladder transitional cell carcinoma  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Colon adenoma  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Colon cancer  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Colon cancer stage 0  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Endometrial cancer  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Gastrointestinal tract adenoma  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Lipoma  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Lung adenocarcinoma  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Non-Hodgkin's lymphoma  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Non-small cell lung cancer stage IIIB  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Ovarian adenoma  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Ovarian cancer  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Rectal cancer metastatic  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Renal oncocytoma  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Small cell lung cancer stage unspecified  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Squamous cell carcinoma of skin  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  1/873 (0.11%)  1/878 (0.11%)  3/869 (0.35%) 
Syncope  1  2/873 (0.23%)  0/878 (0.00%)  1/869 (0.12%) 
Dizziness  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Epilepsy  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Headache  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Ischaemic stroke  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Transient ischaemic attack  1  0/873 (0.00%)  2/878 (0.23%)  0/869 (0.00%) 
Carotid artery stenosis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Cerebral infarction  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Haemorrhagic stroke  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Intercostal neuralgia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Neuralgia  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Parkinsonism  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Presyncope  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Radiculopathy  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Tension headache  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
VIIth nerve paralysis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
VIth nerve paralysis  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Vertebrobasilar insufficiency  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Psychiatric disorders       
Bipolar disorder  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Alcohol withdrawal syndrome  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Depressed mood  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Depression  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Schizophrenia  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Renal and urinary disorders       
Renal failure acute  1  1/873 (0.11%)  2/878 (0.23%)  3/869 (0.35%) 
Nephrolithiasis  1  2/873 (0.23%)  2/878 (0.23%)  0/869 (0.00%) 
Renal colic  1  1/873 (0.11%)  1/878 (0.11%)  1/869 (0.12%) 
Calculus urinary  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Diabetic nephropathy  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Urinary retention  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Adenomyosis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Cervical dysplasia  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Cervix disorder  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Cystocele  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Dysmenorrhoea  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Epididymitis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Metrorrhagia  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Ovarian cyst  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Rectocele  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Uterine prolapse  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Uterovaginal prolapse  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  2/873 (0.23%)  0/878 (0.00%)  1/869 (0.12%) 
Pulmonary embolism  1  1/873 (0.11%)  0/878 (0.00%)  1/869 (0.12%) 
Acute pulmonary oedema  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Asthma  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Dyspnoea  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Emphysema  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Granulomatous pneumonitis  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Interstitial lung disease  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Pleuritic pain  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Pulmonary oedema  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Respiratory failure  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Skin and subcutaneous tissue disorders       
Rash maculo-papular  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Vascular disorders       
Hypertension  1  1/873 (0.11%)  3/878 (0.34%)  0/869 (0.00%) 
Hypertensive crisis  1  0/873 (0.00%)  2/878 (0.23%)  1/869 (0.12%) 
Deep vein thrombosis  1  1/873 (0.11%)  1/878 (0.11%)  0/869 (0.00%) 
Aortic aneurysm  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Arterial thrombosis limb  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Embolism  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Femoral artery occlusion  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Iliac artery occlusion  1  0/873 (0.00%)  1/878 (0.11%)  0/869 (0.00%) 
Orthostatic hypotension  1  0/873 (0.00%)  0/878 (0.00%)  1/869 (0.12%) 
Peripheral arterial occlusive disease  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Thrombophlebitis  1  1/873 (0.11%)  0/878 (0.00%)  0/869 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg Metformin + Glipizide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   688/873 (78.81%)   687/878 (78.25%)   668/869 (76.87%) 
Blood and lymphatic system disorders       
Anaemia  1  16/873 (1.83%)  37/878 (4.21%)  32/869 (3.68%) 
Gastrointestinal disorders       
Diarrhoea  1  60/873 (6.87%)  60/878 (6.83%)  63/869 (7.25%) 
Nausea  1  28/873 (3.21%)  32/878 (3.64%)  20/869 (2.30%) 
General disorders       
Fatigue  1  20/873 (2.29%)  19/878 (2.16%)  28/869 (3.22%) 
Asthenia  1  14/873 (1.60%)  15/878 (1.71%)  27/869 (3.11%) 
Infections and infestations       
Upper respiratory tract infection  1  84/873 (9.62%)  90/878 (10.25%)  76/869 (8.75%) 
Nasopharyngitis  1  78/873 (8.93%)  67/878 (7.63%)  61/869 (7.02%) 
Influenza  1  36/873 (4.12%)  36/878 (4.10%)  42/869 (4.83%) 
Urinary tract infection  1  41/873 (4.70%)  33/878 (3.76%)  38/869 (4.37%) 
Bronchitis  1  39/873 (4.47%)  36/878 (4.10%)  36/869 (4.14%) 
Sinusitis  1  26/873 (2.98%)  29/878 (3.30%)  23/869 (2.65%) 
Investigations       
Creatinine renal clearance decreased  1  23/873 (2.63%)  34/878 (3.87%)  32/869 (3.68%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  18/873 (2.06%)  6/878 (0.68%)  91/869 (10.47%) 
Dyslipidaemia  1  22/873 (2.52%)  20/878 (2.28%)  34/869 (3.91%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  54/873 (6.19%)  45/878 (5.13%)  49/869 (5.64%) 
Arthralgia  1  38/873 (4.35%)  42/878 (4.78%)  40/869 (4.60%) 
Pain in extremity  1  28/873 (3.21%)  28/878 (3.19%)  33/869 (3.80%) 
Nervous system disorders       
Headache  1  45/873 (5.15%)  60/878 (6.83%)  46/869 (5.29%) 
Dizziness  1  24/873 (2.75%)  24/878 (2.73%)  29/869 (3.34%) 
Tremor  1  5/873 (0.57%)  3/878 (0.34%)  29/869 (3.34%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  35/873 (4.01%)  26/878 (2.96%)  33/869 (3.80%) 
Vascular disorders       
Hypertension  1  45/873 (5.15%)  67/878 (7.63%)  65/869 (7.48%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
The Week 52 results summarized in herein differ from the Week 52 results summarized in an interim analysis, because the per protocol set (PPS) defined for the final analysis included fewer subjects than the PPS defined for the interim analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00856284     History of Changes
Other Study ID Numbers: SYR-322_305
2008-007444-34 ( Registry Identifier: EudraCT )
U1111-1111-7397 ( Registry Identifier: WHO )
HKCTR-862 ( Registry Identifier: HKUCTR )
DOH-27-0709-2825 ( Registry Identifier: SANCTR )
09/H0703/66 ( Registry Identifier: NRES )
NMRR-09-203-3590 ( Registry Identifier: NMRR )
First Submitted: March 4, 2009
First Posted: March 5, 2009
Results First Submitted: September 25, 2013
Results First Posted: December 3, 2013
Last Update Posted: December 3, 2013