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Study of Safety and Efficacy of PF-04991532 in Subjects With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01338870
Recruitment Status : Completed
First Posted : April 20, 2011
Results First Posted : April 23, 2013
Last Update Posted : April 23, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Placebo
Drug: 25 mg PF-04991532
Drug: 75 mg PF-04991532
Drug: 150 mg PF-04991532
Drug: 300 mg PF-04991532
Drug: Sitagliptin 100 mg
Enrollment 301
Recruitment Details  
Pre-assignment Details All participants received placebo matched to PF-04991532 or placebo matched to sitagliptin tablet orally twice daily along with background metformin immediate release tablets, during the 2-week run-in period. Compliant participants were then randomized to study treatments for 12 weeks.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Period Title: Overall Study
Started 50 49 50 50 52 50
Completed 41 37 39 41 46 44
Not Completed 9 12 11 9 6 6
Reason Not Completed
Lost to Follow-up             0             0             1             0             1             0
Withdrawal by Subject             2             3             4             0             0             2
Other             3             3             3             2             0             2
Protocol Violation             0             2             2             2             1             1
Adverse Event             4             4             1             5             4             1
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg Total
Hide Arm/Group Description Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 50 49 50 50 52 50 301
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 49 participants 50 participants 50 participants 52 participants 50 participants 301 participants
55.7  (8.8) 59.2  (6.8) 56.1  (8.6) 57.2  (8.7) 56.0  (7.7) 55.6  (9.0) 56.6  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 50 participants 50 participants 52 participants 50 participants 301 participants
Female
16
  32.0%
30
  61.2%
21
  42.0%
20
  40.0%
30
  57.7%
15
  30.0%
132
  43.9%
Male
34
  68.0%
19
  38.8%
29
  58.0%
30
  60.0%
22
  42.3%
35
  70.0%
169
  56.1%
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
Hide Description HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4 percent (%) and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication. Here ‘n’ signifies participants who were evaluable at specific time point for each treatment arm respectively.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 50 52 50
Mean (Standard Deviation)
Unit of Measure: percentage of hemoglobin
Baseline (n= 50, 49, 50, 50, 52, 50) 8.11  (1.255) 7.90  (0.939) 7.86  (0.998) 7.93  (1.018) 8.01  (1.064) 8.05  (0.958)
Change at Week 12 (n= 42, 37, 39, 40, 46, 44) -0.30  (0.681) -0.15  (0.593) -0.51  (0.847) -0.36  (0.828) -0.79  (0.743) -0.65  (0.754)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Treatment difference and 80% confidence interval (CI) were based on least squares (LS) mean. A mixed model repeated measure (MMRM) analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7606
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value 0.10
Confidence Interval (2-Sided) 80%
-0.08 to 0.29
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.145
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Treatment difference and 80% CI were based on LS mean. A MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0266
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.28
Confidence Interval (2-Sided) 80%
-0.46 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.142
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Treatment difference and 80% CI were based on LS mean. A MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0440
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.24
Confidence Interval (2-Sided) 80%
-0.42 to -0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.141
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Treatment difference and 80% CI were based on LS mean. A MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.53
Confidence Interval (2-Sided) 80%
-0.71 to -0.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.137
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Treatment difference and 80% CI were based on LS mean. A MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.43
Confidence Interval (2-Sided) 80%
-0.60 to -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.139
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12
Hide Description [Not Specified]
Time Frame Baseline, Week 1, 2, 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here ‘n’ signifies participants who were evaluable at specific time point for each treatment arm respectively.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 50 52 50
Mean (Standard Deviation)
Unit of Measure: milligram/deciliter (mg/dL)
Baseline (n= 50, 49, 50, 50 ,52, 50) 168.41  (51.859) 167.71  (52.401) 161.43  (43.009) 163.38  (44.976) 168.87  (47.630) 170.42  (41.366)
Change at Week 1 (n= 48, 47, 47, 46, 46, 45) 3.69  (24.632) -0.70  (26.644) -3.29  (20.131) -3.75  (19.486) -15.35  (35.673) -18.59  (30.637)
Change at Week 2 (n= 44, 44, 45, 45, 47, 48) -1.31  (21.746) 1.05  (22.186) -3.84  (24.007) -1.68  (26.966) -16.68  (43.620) -20.13  (32.632)
Change at Week 4 (n= 46, 42, 44, 45, 48, 49) 2.00  (36.067) 6.08  (24.687) -6.56  (32.880) 3.61  (36.385) -19.84  (31.334) -18.90  (28.434)
Change at Week 8 (n= 43, 40, 41, 42, 46, 45) 5.63  (26.183) 9.42  (28.172) -4.98  (30.696) 4.43  (28.491) -14.24  (42.128) -17.84  (28.715)
Change at Week 12 (n= 42, 37, 38, 40, 46, 44) 3.41  (34.430) 8.06  (23.298) -6.55  (31.919) 6.20  (38.122) -16.80  (35.765) -16.07  (31.298)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3611
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -5.21
Confidence Interval (2-Sided) 95%
-16.40 to 5.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.700
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0969
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -9.45
Confidence Interval (2-Sided) 95%
-20.61 to 1.71
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.686
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1566
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.10
Confidence Interval (2-Sided) 95%
-19.30 to 3.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.710
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -15.92
Confidence Interval (2-Sided) 95%
-27.06 to -4.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.678
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -21.09
Confidence Interval (2-Sided) 95%
-32.30 to -9.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.712
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9893
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-11.41 to 11.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.852
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4767
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.14
Confidence Interval (2-Sided) 95%
-15.55 to 7.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.814
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6222
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.87
Confidence Interval (2-Sided) 95%
-14.28 to 8.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.816
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0159
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -13.88
Confidence Interval (2-Sided) 95%
-25.16 to -2.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.744
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -18.69
Confidence Interval (2-Sided) 95%
-29.95 to -7.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.735
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5125
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
-7.71 to 15.43
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.895
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1455
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.47
Confidence Interval (2-Sided) 95%
-19.89 to 2.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.815
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8712
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
-10.43 to 12.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.794
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -19.57
Confidence Interval (2-Sided) 95%
-30.77 to -8.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.707
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -19.08
Confidence Interval (2-Sided) 95%
-30.26 to -7.90
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.696
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2488
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.99
Confidence Interval (2-Sided) 95%
-4.90 to 18.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.055
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2084
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -7.56
Confidence Interval (2-Sided) 95%
-19.34 to 4.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.004
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9053
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
-11.01 to 12.43
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.971
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0091
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -15.30
Confidence Interval (2-Sided) 95%
-26.79 to -3.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.853
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -18.62
Confidence Interval (2-Sided) 95%
-30.15 to -7.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.875
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2963
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.50
Confidence Interval (2-Sided) 95%
-5.71 to 18.70
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.217
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1159
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -9.71
Confidence Interval (2-Sided) 95%
-21.82 to 2.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.170
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4413
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.70
Confidence Interval (2-Sided) 95%
-7.28 to 16.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.103
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0099
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -15.30
Confidence Interval (2-Sided) 95%
-26.91 to -3.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.918
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -14.95
Confidence Interval (2-Sided) 95%
-26.69 to -3.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.981
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8
Hide Description HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
Time Frame Baseline, Week 1, 2, 4, 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signify those who were evaluable for this measure and ‘n’ signifies participants who were evaluable at specific time point for each treatment arm respectively.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 48 47 47 46 48 49
Mean (Standard Deviation)
Unit of Measure: percentage of hemoglobin
Change at Week 1 (n= 48, 47, 47, 46, 46, 47) 0.03  (0.496) -0.01  (0.190) -0.07  (0.182) -0.06  (0.227) -0.02  (0.210) -0.14  (0.223)
Change at Week 2 (n= 45, 44, 45, 45, 47, 48) -0.02  (0.481) -0.10  (0.236) -0.08  (0.230) -0.06  (0.342) -0.17  (0.275) -0.21  (0.357)
Change at Week 4 (n= 46, 42, 44, 45, 48, 49) -0.14  (0.558) -0.15  (0.326) -0.26  (0.436) -0.32  (0.525) -0.37  (0.395) -0.40  (0.463)
Change at Week 8 (n= 43, 40, 41, 42, 45, 45) -0.26  (0.615) -0.14  (0.492) -0.40  (0.697) -0.42  (0.708) -0.58  (0.607) -0.54  (0.696)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 1: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1797
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.05
Confidence Interval (2-Sided) 80%
-0.13 to 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 1: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0234
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.19 to -0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 1: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0400
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.10
Confidence Interval (2-Sided) 80%
-0.18 to -0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 1: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1568
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.06
Confidence Interval (2-Sided) 80%
-0.13 to 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.057
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 1: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.18
Confidence Interval (2-Sided) 80%
-0.25 to -0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.058
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 2: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0695
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.10
Confidence Interval (2-Sided) 80%
-0.19 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 2: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0636
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.11
Confidence Interval (2-Sided) 80%
-0.20 to -0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 2: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0512
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.11
Confidence Interval (2-Sided) 80%
-0.20 to -0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 2: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.18
Confidence Interval (2-Sided) 80%
-0.26 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 2: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.22
Confidence Interval (2-Sided) 80%
-0.30 to -0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 4: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2392
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.07
Confidence Interval (2-Sided) 80%
-0.19 to 0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.094
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 4: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0308
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 80%
-0.29 to -0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.091
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 4: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.27
Confidence Interval (2-Sided) 80%
-0.38 to -0.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.091
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 4: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.24
Confidence Interval (2-Sided) 80%
-0.36 to -0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.089
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 4: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.32
Confidence Interval (2-Sided) 80%
-0.44 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.090
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 8: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7854
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.10
Confidence Interval (2-Sided) 80%
-0.06 to 0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.126
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 8: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0778
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.18
Confidence Interval (2-Sided) 80%
-0.33 to -0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.123
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 8: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.31
Confidence Interval (2-Sided) 80%
-0.46 to -0.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.122
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 8: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.37
Confidence Interval (2-Sided) 80%
-0.52 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.119
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 8: Treatment difference and 80% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline, baseline-by-time interaction, baseline-by-treatment interaction, baseline-by-treatment-by-time interaction as the covariates, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.37
Confidence Interval (2-Sided) 80%
-0.52 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.121
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels
Hide Description HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes, and levels of 6.5% or higher indicate diabetes.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signify those who were evaluable for this measure.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 42 37 39 40 46 44
Measure Type: Number
Unit of Measure: percentage of participants
< 6.5% 11.9 8.1 15.4 17.5 17.4 15.9
< 7% 23.8 29.7 38.5 35.0 43.5 36.4
5.Secondary Outcome
Title Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12
Hide Description Overweight or obesity increases the risk for developing diabetes. The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c.
Time Frame Baseline, Week 1, 2, 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here ‘n’ signifies participants who were evaluable at specific time point for each treatment arm respectively.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 50 52 50
Mean (Standard Deviation)
Unit of Measure: kilogram (kg)
Baseline (n= 50, 49, 50, 50, 52, 50) 89.69  (17.571) 87.24  (19.805) 85.69  (19.805) 85.44  (18.305) 91.61  (21.822) 91.00  (21.013)
Change at Week 1 (n= 48, 47, 47, 46, 47, 47) 0.01  (0.792) -0.20  (1.170) 0.14  (1.600) -0.20  (0.861) -0.20  (1.168) -0.33  (2.089)
Change at Week 2 (n= 45, 44, 45, 45, 47, 48) 0.31  (2.041) -0.49  (1.462) 0.07  (1.510) -0.25  (1.086) -0.03  (1.414) -0.32  (2.488)
Change at Week 4 (n= 46, 42, 44, 45, 48, 49) -0.10  (1.255) -0.55  (1.576) 0.20  (1.594) -0.27  (1.381) -0.58  (1.401) -0.30  (2.276)
Change at Week 8 (n= 43, 40, 41, 42, 46, 45) -0.21  (1.848) -0.57  (1.488) -0.04  (2.318) -0.64  (1.538) -0.67  (1.649) -0.61  (2.648)
Change at Week 12 (n= 42, 37, 39, 41, 46, 44) -0.30  (1.869) -0.71  (1.980) -0.15  (2.757) -0.83  (2.099) -0.75  (2.087) -0.83  (3.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5636
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.69 to 0.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.272
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4889
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.35 to 0.72
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.271
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5849
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.68 to 0.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.272
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5104
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.70 to 0.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.268
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 1: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2640
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.83 to 0.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.269
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0464
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.71
Confidence Interval (2-Sided) 95%
-1.42 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.357
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7107
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.83 to 0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.353
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1564
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.19 to 0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.352
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3834
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.98 to 0.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.345
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 2: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1279
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-1.21 to 0.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.346
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2520
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-1.06 to 0.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.339
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2772
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
-0.30 to 1.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.336
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7038
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.79 to 0.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.335
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2031
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-1.07 to 0.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.329
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 4: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6948
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.78 to 0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.330
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5691
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-1.07 to 0.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.421
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3447
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.42 to 1.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.415
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5769
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-1.04 to 0.58
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.413
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3599
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.16 to 0.42
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.402
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 8: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4600
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-1.10 to 0.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.407
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 25 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4253
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-1.39 to 0.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.504
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 75 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4349
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.59 to 1.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.497
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 150 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6697
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.18 to 0.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.492
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, PF-04991532 300 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5501
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-1.22 to 0.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.476
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg
Comments Week 12: Treatment difference and 95% CI were based on LS mean. MMRM analysis was performed with treatment, time and treatment-by-time interaction as fixed effects, baseline as the covariate, time was repeated for participant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4081
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-1.35 to 0.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.484
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Gain in Body Weight From Baseline
Hide Description Overweight or obesity increases the risk for developing diabetes. Participants with >= 1% or >= 2% gain in body weight from baseline signifies a higher risk of diabetes.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signify those who were evaluable for this measure.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 42 37 39 41 46 44
Measure Type: Number
Unit of Measure: percentage of participants
>= 1% 23.81 27.03 38.46 21.95 15.22 31.82
>= 2% 2.38 2.70 15.38 7.32 6.52 15.91
7.Secondary Outcome
Title Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Loss in Body Weight From Baseline
Hide Description The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c. Participants with >= 1% or >= 2% loss in body weight from baseline signifies an improvement of glycemia.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signify those who were evaluable for this measure.
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description:
Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
Overall Number of Participants Analyzed 42 37 39 41 46 44
Measure Type: Number
Unit of Measure: percentage of participants
>= 1% 38.10 35.14 30.77 48.78 41.30 40.91
>= 2% 23.81 27.03 17.95 26.83 30.43 29.55
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Hide Arm/Group Description Placebo matched to PF-04991532 tablets orally twice daily or placebo matched to sitagliptin tablet orally twice daily along with background metformin 500 milligram (mg) immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 25 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 75 mg tablet orally twice daily along background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 150 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. PF-04991532 300 mg tablet orally twice daily along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks. Sitagliptin 100 mg tablet orally once daily as morning dose and placebo matched to sitagliptin tablet orally once daily as evening dose along with background metformin 500 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization), for 12 weeks.
All-Cause Mortality
Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/50 (0.00%)   0/49 (0.00%)   0/50 (0.00%)   0/50 (0.00%)   0/52 (0.00%)   0/50 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo PF-04991532 25 mg PF-04991532 75 mg PF-04991532 150 mg PF-04991532 300 mg Sitagliptin 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/50 (28.00%)   16/49 (32.65%)   14/50 (28.00%)   11/50 (22.00%)   15/52 (28.85%)   11/50 (22.00%) 
Gastrointestinal disorders             
Diarrhoea * 1  2/50 (4.00%)  0/49 (0.00%)  3/50 (6.00%)  1/50 (2.00%)  2/52 (3.85%)  0/50 (0.00%) 
Infections and infestations             
Nasopharyngitis * 1  0/50 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  1/50 (2.00%)  1/52 (1.92%)  4/50 (8.00%) 
Pharyngitis * 1  1/50 (2.00%)  2/49 (4.08%)  2/50 (4.00%)  1/50 (2.00%)  4/52 (7.69%)  0/50 (0.00%) 
Upper respiratory tract infection * 1  3/50 (6.00%)  1/49 (2.04%)  3/50 (6.00%)  2/50 (4.00%)  2/52 (3.85%)  1/50 (2.00%) 
Urinary tract infection * 1  5/50 (10.00%)  1/49 (2.04%)  2/50 (4.00%)  3/50 (6.00%)  0/52 (0.00%)  2/50 (4.00%) 
Metabolism and nutrition disorders             
Hyperglycaemia * 1  3/50 (6.00%)  5/49 (10.20%)  0/50 (0.00%)  3/50 (6.00%)  1/52 (1.92%)  1/50 (2.00%) 
Hypoglycaemia * 1  0/50 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  1/50 (2.00%)  1/52 (1.92%)  3/50 (6.00%) 
Nervous system disorders             
Dizziness * 1  0/50 (0.00%)  3/49 (6.12%)  0/50 (0.00%)  0/50 (0.00%)  1/52 (1.92%)  0/50 (0.00%) 
Headache * 1  0/50 (0.00%)  4/49 (8.16%)  4/50 (8.00%)  1/50 (2.00%)  3/52 (5.77%)  1/50 (2.00%) 
Vascular disorders             
Hypertension * 1  1/50 (2.00%)  1/49 (2.04%)  2/50 (4.00%)  0/50 (0.00%)  3/52 (5.77%)  0/50 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v15.0
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01338870     History of Changes
Other Study ID Numbers: B2611003
First Submitted: April 13, 2011
First Posted: April 20, 2011
Results First Submitted: March 11, 2013
Results First Posted: April 23, 2013
Last Update Posted: April 23, 2013