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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01338870
• Collaborator: (none)
• Enrollment: 301
• Locations: 42
• Arms: 6
• Duration (Months): 9
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

B2611003 is designed to study how safe and effective an investigational medication (PF-04991532) is in people with Type 2 diabetes. Subjects in the study will receive 1 of 6 treatments for 3 months. One of the treatments will be sitagliptin which is an approved drug, and another treatment will be placebo, which does not contain active ingredient.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	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	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week, Phase 2, Randomized, Double-blind, Placebo Controlled, Dose-ranging, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily Pf-04991532 and Once Daily Sitagliptin in Adult Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo for PF-04991532 and sitagliptin	Drug: Placebo; Tablets (n=4), 0 mg twice daily for 84 days
Experimental: 25 mg PF-04991532	Drug: 25 mg PF-04991532; Tablets (n=1), 25 mg strength + tablets (n=3) 0 mg twice daily for 84 days
Experimental: 75 mg PF-04991532	Drug: 75 mg PF-04991532; Tablets (n=3), 25 mg strength + tablets (n=1) 0 mg twice daily for 84 days
Experimental: 150 mg PF-04991532	Drug: 150 mg PF-04991532; Tablets (n=1), 150 mg strength + tablets (n=3) 0 mg twice daily for 84 days
Experimental: 300 mg PF-04991532	Drug: 300 mg PF-04991532; Tablets (n=2), 150 mg strength + tablets (n=2) 0 mg twice daily for 84 days
Active Comparator: Sitagliptin 100 mg	Drug: Sitagliptin 100 mg; Tablets (n=1), 100 mg strength + tablets (n=3) 0 mg once daily in the morning for 84 days; and tablets (n=4) 0 mg once daily in the evening for 84 days.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 [Baseline, Week 12]

   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.

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12 [Baseline, Week 1, 2, 4, 8, 12]

2. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8 [Baseline, Week 1, 2, 4, 8]

   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.

3. Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels [Week 12]

   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.

4. Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12 [Baseline, Week 1, 2, 4, 8, 12]

   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.

5. Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Gain in Body Weight From Baseline [Week 12]

   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.

6. Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Loss in Body Weight From Baseline [Week 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects with type 2 diabetes on stable doses of background medicines for management of diabetes; aged 18-70 years; body mass index between 22.5 and 45.5 kg/m2

Exclusion Criteria:

Subjects with type 1 diabetes, heart attack or stroke in the past 6 months, uncontrolled blood pressure, significant kidney disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Little Rock	Arkansas	United States	72205
2	Pfizer Investigational Site	Roseville	California	United States	95661
3	Pfizer Investigational Site	Denver	Colorado	United States	80209
4	Pfizer Investigational Site	Coral Gables	Florida	United States	33134
5	Pfizer Investigational Site	Ocala	Florida	United States	34471
6	Pfizer Investigational Site	Honolulu	Hawaii	United States	96814
7	Pfizer Investigational Site	Indianapolis	Indiana	United States	46260
8	Pfizer Investigational Site	Augusta	Kansas	United States	67010
9	Pfizer Investigational Site	Overland Park	Kansas	United States	66215
10	Pfizer Investigational Site	Wichita	Kansas	United States	67207
11	Pfizer Investigational Site	Lexington	Kentucky	United States	40504
12	Pfizer Investigational Site	Lake Charles	Louisiana	United States	70601
13	Pfizer Investigational Site	Auburn	Maine	United States	04210
14	Pfizer Investigational Site	Brooklyn Center	Minnesota	United States	55430
15	Pfizer Investigational Site	Las Vegas	Nevada	United States	89101
16	Pfizer Investigational Site	Trenton	New Jersey	United States	08611
17	Pfizer Investigational Site	Charlotte	North Carolina	United States	28277
18	Pfizer Investigational Site	Fargo	North Dakota	United States	58103
19	Pfizer Investigational Site	Cincinnati	Ohio	United States	45245
20	Pfizer Investigational Site	Lansdale	Pennsylvania	United States	19446
21	Pfizer Investigational Site	Dallas	Texas	United States	75246
22	Pfizer Investigational Site	Katy	Texas	United States	77450
23	Pfizer Investigational Site	San Antonio	Texas	United States	78229
24	Pfizer Investigational Site	Norfolk	Virginia	United States	23502
25	Pfizer Investigational Site	Richmond	Virginia	United States	23294
26	Pfizer Investigational Site	Surrey	British Columbia	Canada	V4A 2H9
27	Pfizer Investigational Site	Bay Roberts	Newfoundland and Labrador	Canada	A0A 1G0
28	Pfizer Investigational Site	Brampton	Ontario	Canada	L6T 0G1
29	Pfizer Investigational Site	Mississauga	Ontario	Canada	L4Y 2N8
30	Pfizer Investigational Site	Mirabel	Quebec	Canada	J7J 2K8
31	Pfizer Investigational Site	Quebec		Canada	G3K 2P8
32	Pfizer Investigational Site	Balatonfured		Hungary	8230
33	Pfizer Investigational Site	Kistelek		Hungary	6760
34	Pfizer Investigational Site	Mexico	DF	Mexico	06700
35	Pfizer Investigational Site	Tlalnepantla	Estado de Mexico	Mexico	54055
36	Pfizer Investigational Site	Aguascalientes		Mexico	20234
37	Pfizer Investigational Site	Bratislava		Slovakia	851 01
38	Pfizer Investigational Site	Nove Mesto nad Vahom		Slovakia	915 01
39	Pfizer Investigational Site	Pezinok		Slovakia	902 01
40	Pfizer Investigational Site	Presov		Slovakia	080 01
41	Pfizer Investigational Site	Taichung		Taiwan	40705
42	Pfizer Investigational Site	Taoyuan County		Taiwan	333

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01338870
• Other Study ID Numbers: B2611003
• First Posted: Apr 20, 2011
• Last Update Posted: Apr 23, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Pfizer: Phase 2; safety and efficacy study with PF-04991532; Type 2 diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Nicotinic Acids; Sitagliptin Phosphate; 6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid

Study Results

Participant Flow

Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Placebo	PF-04991532 25 mg	PF-04991532 75 mg	PF-04991532 150 mg	PF-04991532 300 mg	Sitagliptin 100 mg	Total
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 Participants	50	49	50	50	52	50	301
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	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 (Count of Participants)
Female	16 32%	30 61.2%	21 42%	20 40%	30 57.7%	15 30%	132 43.9%
Male	34 68%	19 38.8%	29 58%	30 60%	22 42.3%	35 70%	169 56.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
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

Outcome Measure Data

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
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.
Measure Participants	50	49	50	50	52	50
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)

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
Statistical Test of Hypothesis	p-Value	0.7606
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0266
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0440
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Mixed Models Analysis
	Comments
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

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12
Time Frame	Baseline, Week 1, 2, 4, 8, 12

Outcome Measure Data

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
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.
Measure Participants	50	49	50	50	52	50
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)

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
Statistical Test of Hypothesis	p-Value	0.3611
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0969
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1566
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0052
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.9893
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4767
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.6222
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0159
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5125
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1455
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.8712
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2488
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2084
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.9053
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0091
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2963
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1159
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4413
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0099
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0126
	Comments
	Method	Mixed Models Analysis
	Comments
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

3. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8
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

Outcome Measure Data

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
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.
Measure Participants	48	47	47	46	48	49
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)

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
Statistical Test of Hypothesis	p-Value	0.1797
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0234
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0400
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1568
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0695
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0636
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0512
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0051
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2392
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0308
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.7854
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0778
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0065
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Mixed Models Analysis
	Comments
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

4. Secondary Outcome

Title	Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels
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

Outcome Measure Data

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
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.
Measure Participants	42	37	39	40	46	44
< 6.5%	11.9 23.8%	8.1 16.5%	15.4 30.8%	17.5 35%	17.4 33.5%	15.9 31.8%
< 7%	23.8 47.6%	29.7 60.6%	38.5 77%	35.0 70%	43.5 83.7%	36.4 72.8%

5. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12
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

Outcome Measure Data

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
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.
Measure Participants	50	49	50	50	52	50
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)

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
Statistical Test of Hypothesis	p-Value	0.5636
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4889
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5849
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5104
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2640
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.0464
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.7107
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1564
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.3834
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.1279
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2520
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2772
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.7038
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.2031
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.6948
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5691
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.3447
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5769
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.3599
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4600
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4253
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4349
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.6697
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.5501
	Comments
	Method	Mixed Models Analysis
	Comments
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

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
Statistical Test of Hypothesis	p-Value	0.4081
	Comments
	Method	Mixed Models Analysis
	Comments
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

6. Secondary Outcome

Title	Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Gain in Body Weight From Baseline
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

Outcome Measure Data

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
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.
Measure Participants	42	37	39	41	46	44
>= 1%	23.81 47.6%	27.03 55.2%	38.46 76.9%	21.95 43.9%	15.22 29.3%	31.82 63.6%
>= 2%	2.38 4.8%	2.70 5.5%	15.38 30.8%	7.32 14.6%	6.52 12.5%	15.91 31.8%

7. Secondary Outcome

Title	Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Loss in Body Weight From Baseline
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

Outcome Measure Data

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
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.
Measure Participants	42	37	39	41	46	44
>= 1%	38.10 76.2%	35.14 71.7%	30.77 61.5%	48.78 97.6%	41.30 79.4%	40.91 81.8%
>= 2%	23.81 47.6%	27.03 55.2%	17.95 35.9%	26.83 53.7%	30.43 58.5%	29.55 59.1%

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/49 (0%)		0/50 (0%)		0/50 (0%)		0/52 (0%)		0/50 (0%)
Other (Not Including 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/50 (28%)		16/49 (32.7%)		14/50 (28%)		11/50 (22%)		15/52 (28.8%)		11/50 (22%)
Gastrointestinal disorders
Diarrhoea	2/50 (4%)		0/49 (0%)		3/50 (6%)		1/50 (2%)		2/52 (3.8%)		0/50 (0%)
Infections and infestations
Nasopharyngitis	0/50 (0%)		1/49 (2%)		0/50 (0%)		1/50 (2%)		1/52 (1.9%)		4/50 (8%)
Pharyngitis	1/50 (2%)		2/49 (4.1%)		2/50 (4%)		1/50 (2%)		4/52 (7.7%)		0/50 (0%)
Upper respiratory tract infection	3/50 (6%)		1/49 (2%)		3/50 (6%)		2/50 (4%)		2/52 (3.8%)		1/50 (2%)
Urinary tract infection	5/50 (10%)		1/49 (2%)		2/50 (4%)		3/50 (6%)		0/52 (0%)		2/50 (4%)
Metabolism and nutrition disorders
Hyperglycaemia	3/50 (6%)		5/49 (10.2%)		0/50 (0%)		3/50 (6%)		1/52 (1.9%)		1/50 (2%)
Hypoglycaemia	0/50 (0%)		1/49 (2%)		0/50 (0%)		1/50 (2%)		1/52 (1.9%)		3/50 (6%)
Nervous system disorders
Dizziness	0/50 (0%)		3/49 (6.1%)		0/50 (0%)		0/50 (0%)		1/52 (1.9%)		0/50 (0%)
Headache	0/50 (0%)		4/49 (8.2%)		4/50 (8%)		1/50 (2%)		3/52 (5.8%)		1/50 (2%)
Vascular disorders
Hypertension	1/50 (2%)		1/49 (2%)		2/50 (4%)		0/50 (0%)		3/52 (5.8%)		0/50 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.