A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02554877
• Collaborator: (none)
• Enrollment: 206
• Locations: 38
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether PF-06291874 is effective in the treatment T2DM

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: PF-06291874; Drug: Placebo	Phase 2

Detailed Description

This will be a randomized, double blind, stratified, placebo controlled, parallel group study conducted in T2DM subjects receiving background metformin therapy. Subjects will complete screening procedures to determine eligibility, followed by an 8 week metformin stabilization period prior to randomization. In addition, subjects taking other OADs, in combination with metformin, will undergo a washout during this period, in which non metformin OAD medications will be temporarily discontinued for the duration of the trial. Following confirmation of study eligibility criteria at randomization, subjects will be stratified into 2 groups based on the use of concomitant statin therapy. Each stratum will be randomized across treatment groups, such that the number of subjects taking concomitant statin therapy and those not taking statin therapy will be approximately balanced across treatment groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 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, Parallel Group Study To Evaluate The Efficacy And Safety Of Once Daily Pf-06291874 Administration In Adults With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; oral tablet
Experimental: PF-06291874, 30 mg	Drug: PF-06291874; study drug to be given as an oral tablet at 30, 60 or 100 mg
Experimental: PF-06291874, 60 mg	Drug: PF-06291874; study drug to be given as an oral tablet at 30, 60 or 100 mg
Experimental: PF-06291874, 100 mg	Drug: PF-06291874; study drug to be given as an oral tablet at 30, 60 or 100 mg

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo [Baseline, Week 12]

   HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study.

Secondary Outcome Measures

1. Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8 [Baseline, Weeks 2, 4, 8]

   HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study. n represented the available number of participants for analysis at post-baseline days.

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

   Fasting plasma glucose response changed from baseline at Weeks 2,4,8 and 12. Baseline was defined as the average of the measurements obtained during Day 14 visit window and Day 1 pre-dose measurement. n represented the available number of participants for analysis at post-baseline days.

3. Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12. [Week 12]

   HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

4. Number of Participants With Laboratory Test Abnormalities [Baseline up to 98 days]

   The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.

5. Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria [Baseline up to Day 98]

   ECG criteria of potential clinical concern were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): >=140 milliseconds (msec); >=50% increase from baseline; 2), the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): >=300 msec; >=25 percent (%) increase when baseline >200 msec; or increase >=50% when baseline less than or equal to (<=)200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >=500 msec; increase from baseline >=30 - <60, >=60 msec.

6. Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria [Baseline up to Day 98]

   Vital signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), pulse rate <40 or greater than (>) 120 beats per minute (bpm).

7. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs). [Baseline up to Day 119]

   An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug; the event need not necessarily have a causal relationship with the treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reasons: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. Any events occurring following start of treatment (defined as blinded therapy, including single blind placebo administration on Day 14) or increasing in severity were counted as treatment emergent AE.

8. Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12 [Baseline, Weeks 2, 4, 8 and 12]

   Fasting low density lipoprotein-cholesterol (LDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

9. Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12 [Baseline, Weeks 2, 4, 8 and 12]

   Triglycerides percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days. Triglycerides MMRM was not appropriate as the data were very skewed and not normally distributed, therefore per SAP non-parametric analysis were reported, presenting medians and CIs for medians, instead. If the data had many outliers even after the log transformation the following non parametric analysis was presented instead of the MMRM. An outlier was defined as any data point falling outside of 3.5 x standard deviations the median.

10. Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12 [Baseline, Weeks 2, 4, 8 and 12]

    Total cholesterol percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

11. Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12 [Baseline, Weeks 2, 4, 8 and 12]

    High density lipoprotein-cholesterol (HDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

12. Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12 [Baseline, Weeks 2, 4, 8 and 12]

    Non-HDL-C percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

13. Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12. [Baseline, Weeks 2, 4, 8 and 12]

    The body weight change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Males or non-childbearing potential females between the ages of 18 (or the minimum country specific age of consent if >18) and 70 years, inclusive, at the screening visit (V1) with the diagnosis of T2DM;Female subjects who are not of childbearing potential

2. Subjects who have been on a stable dose of metformin either alone or in combination with one additional acceptable OAD

3. HbA1c at the Screen Visit (V1), as assessed by study specific central laboratory, is 7-11% if on metformin monotherapy; is 6.5-9.5% if on dual combination therapy (metformin plus 1)

Exclusion Criteria:

1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;

2. Fasting plasma glucose levels >270 mg/dL (15.0 mmol/L) at the screening and run in visit, (as assessed by study specific central laboratory) confirmed by a single repeat, if deemed necessary

3. History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class III IV heart failure, or transient ischemic attack within 6 months of screening;

4. Any medical condition possibly affecting study drug absorption (eg, gastrectomy or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency

5. Subjects with a creatinine clearance <60 mL/min as determined by the Cockcroft Gault equation (listed below) using serum creatinine measured at screening, confirmed via a single repeat, if deemed necessary

6. Subject with a positive result for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Ab) or hepatitis C virus (HCV) antibodies

7. Screening seated systolic blood pressure >160 mm Hg and/or diastolic blood pressure

105 mm Hg after at least a 5 minute rest. Blood pressure determined as the mean of triplicate measurements collected with approximately 2 minutes of rest between measurements

1. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) >470 msec; or a QRS interval >120 msec. If QTc exceeds 470 msec or QRS exceeds 120 msec, the ECG may be repeated 2 more times with an interval of 2-4 minutes between each measurement and the mean of the 3 values used to determine the subject's eligibility

2. Subjects with an arm circumference >52 cm measured at the midpoint of the length of the upper arm;

3. History (within the last 6 months) of regular alcohol consumption exceeding 14 drinks per week for men and 7 drinks a week for women. (1 drink = 5 ounces of wine (150 mL) or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor);

4. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to V1;

5. Subjects with a known hypersensitivity or intolerance to a glucagon receptor antagonist, or known prior participation in a trial involving PF 06291874;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
2	National Research Institute	Los Angeles	California	United States	90057
3	NRC Research Institute	Orange	California	United States	92868
4	Sierra Clinical Research	Roseville	California	United States	95661
5	Encompass Clinical Research	Spring Valley	California	United States	91978
6	Empire Clinical Research	Upland	California	United States	91786
7	Diablo Clinical Research, Inc	Walnut Creek	California	United States	94598
8	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
9	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
10	Suncoast Research Group, Llc	Miami	Florida	United States	33135
11	QPS-MRA, LLC (Miami Research Associates)	South Miami	Florida	United States	33143
12	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
13	WR-Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia	United States	30328
14	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
15	Midwest Institute for Clinical Research	Indianapolis	Indiana	United States	46260
16	Crescent City Clinical Research Center, LLC	Metairie	Louisiana	United States	70006
17	St. Louis Clinical Trials, LC	Saint Louis	Missouri	United States	63141
18	ALAS Science Clinical Research	Las Vegas	Nevada	United States	89120
19	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
20	Clinilabs Inc.	Eatontown	New Jersey	United States	07724
21	Pharmaceutical Research Associates, Inc.	Marlton	New Jersey	United States	08053
22	TLB Research	Trenton	New Jersey	United States	08611
23	Randolph Medical Associates	Asheboro	North Carolina	United States	27203
24	High Point Clinical Trials Center, LLC	High Point	North Carolina	United States	27265
25	Lillestol Research, LLC	Fargo	North Dakota	United States	58103
26	Aventiv Research	Columbus	Ohio	United States	43213
27	Juno Research, LLC	Houston	Texas	United States	77074
28	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
29	Juno Research, LLC	Katy	Texas	United States	77450
30	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
31	Northeast Clinical Research of San Antonio, LLC	Schertz	Texas	United States	78154
32	National Clinical Research - Richmond, Inc.	Richmond	Virginia	United States	23294
33	Aggarwal and Associates Limited	Brampton	Ontario	Canada	L6T 0G1
34	LMC Clinical Research Inc. (Thornhill)	Thornhill	Ontario	Canada	L4J 8L7
35	LMC Clinical Research Inc. (Bayview)	Toronto	Ontario	Canada	M4G 3E8
36	Manna Research	Toronto	Ontario	Canada	M9W 4L6
37	Manna Research Inc.	Lévis	Quebec	Canada	G6W 0M6
38	Omnispec Clinical Research, Inc.	Mirabel	Quebec	Canada	J7J 2K8

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: NCT02554877
• Other Study ID Numbers: B4801010
• First Posted: Sep 18, 2015
• Last Update Posted: Aug 7, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Period Title: Overall Study
STARTED	51	51	52	52
COMPLETED	39	44	46	45
NOT COMPLETED	12	7	6	7

Baseline Characteristics

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg	Total
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Total of all reporting groups
Overall Participants	51	51	52	52	206
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (6.3)	58.1 (6.9)	57.1 (7.1)	57.4 (7.9)	57.3 (7)
Sex: Female, Male (Count of Participants)
Female	22 43.1%	20 39.2%	24 46.2%	21 40.4%	87 42.2%
Male	29 56.9%	31 60.8%	28 53.8%	31 59.6%	119 57.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo
Description	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	39	44	46	45
Mean (Standard Deviation) [percentage of HbA1c]	0.18 (0.834)	-0.68 (0.778)	-0.91 (0.765)	-0.92 (0.809)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from mixed model for repeated measurements (MMRM) with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95%; -1.34 to -0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from mixed model for repeated measurements (MMRM) with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -1.59 to -0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from mixed model for repeated measurements (MMRM) with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.17
	Confidence Interval	(2-Sided) 95%; -1.60 to -0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8
Description	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Baseline was defined as the last pre-dose measurement prior to first double blind dosing for the study. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 HbA1c(%)Change from Baseline(n=46,48,48,47)	0.10 (0.363)	-0.30 (0.383)	-0.30 (0.341)	-0.31 (0.260)
Week 4 HbA1c(%)Change from Baseline(n=45,47,47,47)	0.12 (0.426)	-0.53 (0.546)	-0.57 (0.444)	-0.49 (0.371)
Week 8 HbA1c(%)Change from Baseline(n=40,45,47,45)	0.15 (0.653)	-0.65 (0.617)	-0.90 (0.612)	-0.82 (0.512)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects
	Method	ANCOVA
	Comments	Least squares mean (LS mean) difference from placebo adjusted for baseline values was derived from the ANCOVA model
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.52 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.52 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.79 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -0.93 to -0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects..
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.17 to -0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from analysis of covariance (ANCOVA) model with baseline value and treatment group as fixed effects.
	Method	ANCOVA
	Comments	LS mean difference from placebo adjusted for baseline values was derived from the ANCOVA model.
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.20 to -0.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12
Description	Fasting plasma glucose response changed from baseline at Weeks 2,4,8 and 12. Baseline was defined as the average of the measurements obtained during Day 14 visit window and Day 1 pre-dose measurement. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2,4,8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who had received at least 1 dose of randomized treatment. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Change from Baseline(n=49,48,48,47)	11.0 (28.5)	-25.2 (26.95)	-32.4 (35.31)	-32.5 (32.26)
Week 4 Change from Baseline(n=45,47,47,47)	3.4 (29.22)	-26.8 (29.68)	-34.7 (39.15)	-30.9 (32.55)
Week 8 Change from Baseline(n=39,44,47,45)	-1.8 (42.57)	-19.9 (35.93)	-35.4 (32.5)	-31.8 (26.57)
Week 12 Change from Baseline(n=39,43,46,45)	-0.6 (31.64)	-18.5 (30.19)	-32.8 (35.24)	-31.9 (35.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-37.83
	Confidence Interval	(2-Sided) 95%; -47.96 to -27.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-44.85
	Confidence Interval	(2-Sided) 95%; -54.98 to -34.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.13
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-48.59
	Confidence Interval	(2-Sided) 95%; -58.81 to -38.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.18
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-30.63
	Confidence Interval	(2-Sided) 95%; -42.52 to -18.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.03
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-39.24
	Confidence Interval	(2-Sided) 95%; -51.13 to -27.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.03
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-38.30
	Confidence Interval	(2-Sided) 95%; -50.22 to -26.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.04
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-19.47
	Confidence Interval	(2-Sided) 95%; -31.88 to -7.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.29
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-36.98
	Confidence Interval	(2-Sided) 95%; -49.27 to -24.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.23
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-35.14
	Confidence Interval	(2-Sided) 95%; -47.55 to -22.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.29
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-19.77
	Confidence Interval	(2-Sided) 95%; -31.81 to -7.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.10
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-35.26
	Confidence Interval	(2-Sided) 95%; -47.17 to -23.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.03
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-36.44
	Confidence Interval	(2-Sided) 95%; -48.43 to -24.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.07
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.
Description	HbA1c was a form of hemoglobin which was measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	39	44	46	45
HbA1c <6.5%	5.13 10.1%	11.36 22.3%	13.04 25.1%	22.22 42.7%
HbA1c <7%	15.38 30.2%	29.55 57.9%	34.78 66.9%	55.56 106.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<7%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.057
	Confidence Interval	(2-Sided) 95%; 1.68 to 21.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<7%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.927
	Confidence Interval	(2-Sided) 95%; 2.49 to 31.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<7%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	15.116
	Confidence Interval	(2-Sided) 95%; 4.34 to 52.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<6.5%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1532
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.340
	Confidence Interval	(2-Sided) 95%; 0.64 to 17.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<6.5%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0826
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	4.198
	Confidence Interval	(2-Sided) 95%; 0.83 to 21.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12 (HbA1C<6.5%)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0272
	Comments	P-value was derived from the logistic regression model with treatment (categorical) and baseline HbA1c as covariate.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.588
	Confidence Interval	(2-Sided) 95%; 1.21 to 25.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities
Description	The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.
Time Frame	Baseline up to 98 days

Outcome Measure Data

Analysis Population Description

The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	49	51	50
Number [participants]	49 96.1%	42 82.4%	40 76.9%	38 73.1%

6. Secondary Outcome

Title	Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria
Description	ECG criteria of potential clinical concern were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): >=140 milliseconds (msec); >=50% increase from baseline; 2), the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): >=300 msec; >=25 percent (%) increase when baseline >200 msec; or increase >=50% when baseline less than or equal to (<=)200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >=500 msec; increase from baseline >=30 - <60, >=60 msec.
Time Frame	Baseline up to Day 98

Outcome Measure Data

Analysis Population Description

The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	48	50	50
Maximum PR interval >=300 msec	0 0%	0 0%	0 0%	0 0%
Maximum QRS interval >=140 msec	0 0%	0 0%	0 0%	1 1.9%
Maximum QTcF interval 450-<480 msec	4 7.8%	4 7.8%	2 3.8%	2 3.8%
Maximum PR interval increase >=25%/50%	0 0%	0 0%	1 1.9%	1 1.9%
Maximum QRS complex increase >=50%	1 2%	0 0%	0 0%	0 0%
Maximum QTcF interval increase 30<=-<60 msec	1 2%	0 0%	3 5.8%	5 9.6%
Maximum QTcF interval increase >=60 msec	0 0%	1 2%	0 0%	0 0%
Maximum QTcF interval 480-<500 msec	0 0%	0 0%	0 0%	0 0%
Maximum QTcF interval >=500 msec	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria
Description	Vital signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), pulse rate <40 or greater than (>) 120 beats per minute (bpm).
Time Frame	Baseline up to Day 98

Outcome Measure Data

Analysis Population Description

The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	49	51	50
Sitting SBP <90 mm Hg	1 2%	0 0%	0 0%	0 0%
Sitting DBP <50mm Hg	1 2%	0 0%	0 0%	0 0%
Sitting Pulse Rate <40 bpm	0 0%	0 0%	0 0%	0 0%
Sitting Pulse Rate >120 bpm	0 0%	0 0%	0 0%	0 0%
Increase: Sitting SBP >=30 mm Hg	0 0%	3 5.9%	1 1.9%	4 7.7%
Increase: Sitting Systolic BP >=20 mm Hg	0 0%	1 2%	0 0%	3 5.8%
Decrease: Sitting SBP >=30 mm Hg	1 2%	2 3.9%	1 1.9%	0 0%
Decrease: Sitting SBP >=20 mm Hg	0 0%	0 0%	1 1.9%	0 0%

8. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).
Description	An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug; the event need not necessarily have a causal relationship with the treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reasons: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. Any events occurring following start of treatment (defined as blinded therapy, including single blind placebo administration on Day 14) or increasing in severity were counted as treatment emergent AE.
Time Frame	Baseline up to Day 119

Outcome Measure Data

Analysis Population Description

The safety analysis set was used, which defined as all participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
AEs	22 43.1%	20 39.2%	18 34.6%	27 51.9%
SAEs	2 3.9%	1 2%	0 0%	2 3.8%
HAEs	5 9.8%	1 2%	1 1.9%	2 3.8%

9. Secondary Outcome

Title	Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12
Description	Fasting low density lipoprotein-cholesterol (LDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Percent Change from Baseline(n=49,47,48,47)	0.68 (16.301)	-1.41 (17.832)	-0.64 (17.154)	2.16 (16.846)
Week 4 Percent Change from Baseline(n=45,47,47,47)	3.29 (18.485)	0.46 (12.752)	-0.62 (18.522)	-2.07 (15.170)
Week 8 Percent Change from Baseline(n=40,45,47,45)	5.31 (21.244)	2.17 (15.503)	1.32 (17.448)	1.92 (17.030)
Week12 Percent Change from Baseline(n=39,43,46,45)	0.13 (18.680)	1.77 (17.278)	4.20 (18.315)	1.16 (19.061)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7618
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 90%; -6.66 to 4.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.40
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8489
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 90%; -6.25 to 4.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.39
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4699
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	2.47
	Confidence Interval	(2-Sided) 90%; -3.17 to 8.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.42
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4979
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-2.22
	Confidence Interval	(2-Sided) 90%; -7.63 to 3.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.27
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2927
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-3.45
	Confidence Interval	(2-Sided) 90%; -8.85 to 1.95
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.27
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1430
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-4.83
	Confidence Interval	(2-Sided) 90%; -10.26 to 0.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.28
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7373
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.25
	Confidence Interval	(2-Sided) 90%; -7.42 to 4.92
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.73
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5075
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-2.46
	Confidence Interval	(2-Sided) 90%; -8.57 to 3.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.70
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6295
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 90%; -7.99 to 4.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.74
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4266
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.15
	Confidence Interval	(2-Sided) 90%; -3.39 to 9.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.95
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2038
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	4.96
	Confidence Interval	(2-Sided) 90%; -1.47 to 11.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.89
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5592
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	2.29
	Confidence Interval	(2-Sided) 90%; -4.19 to 8.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.92
	Estimation Comments

10. Secondary Outcome

Title	Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12
Description	Triglycerides percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days. Triglycerides MMRM was not appropriate as the data were very skewed and not normally distributed, therefore per SAP non-parametric analysis were reported, presenting medians and CIs for medians, instead. If the data had many outliers even after the log transformation the following non parametric analysis was presented instead of the MMRM. An outlier was defined as any data point falling outside of 3.5 x standard deviations the median.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Percent Change from Baseline(n=49,48,48,47)	5.45	10.55	8.32	22.58
Week 4 Percent Change from Baseline(n=44,47,47,47)	3.74	6.45	6.67	1.18
Week 8 Percent Change from Baseline(n=40,45,47,45)	6.72	5.08	2.13	9.47
Week12 Percent Change from Baseline(n=39,44,46,45)	-0.72	7.13	-1.85	5.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	5.09
	Confidence Interval	(2-Sided) 90%; -5.86 to 16.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.86
	Confidence Interval	(2-Sided) 90%; -9.76 to 15.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	17.13
	Confidence Interval	(2-Sided) 90%; 3.91 to 30.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.71
	Confidence Interval	(2-Sided) 90%; -10.80 to 16.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.92
	Confidence Interval	(2-Sided) 90%; -10.61 to 16.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-2.57
	Confidence Interval	(2-Sided) 90%; -15.08 to 9.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.63
	Confidence Interval	(2-Sided) 90%; -16.29 to 13.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-4.59
	Confidence Interval	(2-Sided) 90%; -20.40 to 11.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.75
	Confidence Interval	(2-Sided) 90%; -13.66 to 19.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	7.86
	Confidence Interval	(2-Sided) 90%; -3.30 to 19.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 90%; -16.13 to 13.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	5.99
	Confidence Interval	(2-Sided) 90%; -7.07 to 19.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12
Description	Total cholesterol percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Percent Change from Baseline(n=49,48,48,47)	0.16 (11.863)	0.39 (12.606)	1.02 (12.058)	4.05 (13.900)
Week 4 Percent Change from Baseline(n=44,47,47,47)	2.65 (14.642)	1.69 (8.763)	0.36 (13.732)	0.44 (11.674)
Week 8 Percent Change from Baseline(n=40,45,47,45)	3.30 (14.354)	1.53 (10.569)	-0.11 (12.692)	2.77 (10.860)
Week12 Percent Change from Baseline(n=39,44,46,45)	-0.87 (13.238)	2.28 (12.260)	3.00 (13.952)	2.03 (13.986)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6800
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 90%; -3.12 to 5.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.52
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5150
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 90%; -2.52 to 5.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.52
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0676
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	4.66
	Confidence Interval	(2-Sided) 90%; 0.47 to 8.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.53
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8021
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 90%; -4.73 to 3.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.48
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4346
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.95
	Confidence Interval	(2-Sided) 90%; -6.06 to 2.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.49
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4173
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-2.03
	Confidence Interval	(2-Sided) 90%; -6.15 to 2.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.49
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7036
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 90%; -5.21 to 3.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.56
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2993
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-2.64
	Confidence Interval	(2-Sided) 90%; -6.84 to 1.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.54
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9751
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 90%; -4.16 to 4.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.57
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1408
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	4.23
	Confidence Interval	(2-Sided) 90%; -0.50 to 8.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.86
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0986
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	4.70
	Confidence Interval	(2-Sided) 90%; 0.02 to 9.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.83
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1851
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.79
	Confidence Interval	(2-Sided) 90%; -0.92 to 8.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.85
	Estimation Comments

12. Secondary Outcome

Title	Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12
Description	High density lipoprotein-cholesterol (HDL-C) percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Percent Change from Baseline(n=49,48,48,47)	-0.14 (8.086)	0.08 (9.345)	2.60 (10.739)	8.13 (13.554)
Week 4 Percent Change from Baseline(n=44,47,47,47)	0.51 (11.391)	0.79 (10.626)	3.98 (14.288)	8.16 (11.776)
Week 8 Percent Change from Baseline(n=40,45,47,45)	-1.91 (11.736)	1.24 (10.292)	2.15 (10.724)	7.71 (13.768)
Week12 Percent Change from Baseline(n=39,44,46,45)	-2.62 (13.237)	3.65 (12.889)	4.51 (10.598)	7.57 (15.226)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8559
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 90%; -3.19 to 3.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.17
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1729
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	2.97
	Confidence Interval	(2-Sided) 90%; -0.62 to 6.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.17
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	8.45
	Confidence Interval	(2-Sided) 90%; 4.84 to 12.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.18
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8837
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 90%; -3.85 to 4.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.55
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1573
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.62
	Confidence Interval	(2-Sided) 90%; -0.60 to 7.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.55
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	7.88
	Confidence Interval	(2-Sided) 90%; 3.65 to 12.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.56
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1538
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.59
	Confidence Interval	(2-Sided) 90%; -0.55 to 7.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.51
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0789
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	4.39
	Confidence Interval	(2-Sided) 90%; 0.28 to 8.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.48
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	10.14
	Confidence Interval	(2-Sided) 90%; 5.98 to 14.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.51
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0132
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	6.96
	Confidence Interval	(2-Sided) 90%; 2.36 to 11.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.78
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0079
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	7.41
	Confidence Interval	(2-Sided) 90%; 2.85 to 11.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.75
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	10.83
	Confidence Interval	(2-Sided) 90%; 6.24 to 15.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.77
	Estimation Comments

13. Secondary Outcome

Title	Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12
Description	Non-HDL-C percent change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) on Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Percent Change from Baseline(n=49,48,48,47)	0.51 (16.195)	1.00 (16.675)	0.63 (14.870)	2.73 (18.427)
Week 4 Percent Change from Baseline(n=44,47,47,47)	4.18 (21.486)	1.88 (11.961)	-0.47 (17.972)	-2.40 (13.877)
Week 8 Percent Change from Baseline(n=40,45,47,45)	5.24 (19.222)	1.76 (14.128)	-0.52 (16.014)	0.88 (13.765)
Week12 Percent Change from Baseline(n=39,44,46,45)	-0.48 (16.711)	2.09 (16.451)	2.67 (18.098)	-0.25 (17.666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6597
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 90%; -4.01 to 6.92
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.31
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7583
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; -4.45 to 6.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.31
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3516
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.11
	Confidence Interval	(2-Sided) 90%; -2.39 to 8.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.33
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5877
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-1.83
	Confidence Interval	(2-Sided) 90%; -7.42 to 3.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.38
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2016
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-4.33
	Confidence Interval	(2-Sided) 90%; -9.92 to 1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.38
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0568
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-6.49
	Confidence Interval	(2-Sided) 90%; -12.08 to -0.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.39
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3827
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-2.94
	Confidence Interval	(2-Sided) 90%; -8.48 to 2.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.36
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1126
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-5.31
	Confidence Interval	(2-Sided) 90%; -10.81 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.33
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2160
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	-4.17
	Confidence Interval	(2-Sided) 90%; -9.73 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.36
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3443
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.54
	Confidence Interval	(2-Sided) 90%; -2.64 to 9.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.74
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3031
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	3.82
	Confidence Interval	(2-Sided) 90%; -2.30 to 9.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.70
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8129
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 90%; -5.27 to 7.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.72
	Estimation Comments

14. Secondary Outcome

Title	Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.
Description	The body weight change from baseline (defined as the mean of Day 14 and Day 1 pre-dose) at Weeks 2,4,8 and 12. n represented the available number of participants for analysis at post-baseline days.
Time Frame	Baseline, Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All participants randomized and who received at least 1 dose of randomized treatment, participants were assigned to the randomized treatment regardless of what treatment was received. n represented the available number of participants for analysis at post-baseline days.

Arm/Group Title	Placebo	PF-06291874 30 mg	PF-06291874 60 mg	PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.	Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
Measure Participants	51	51	52	52
Week 2 Change from Baseline(n=49,48,48,47)	-0.15 (1.347)	0.15 (1.234)	-0.15 (1.253)	0.65 (3.342)
Week 4 Change from Baseline(n=45,47,47,47)	-0.76 (3.302)	0.55 (1.231)	0.28 (1.219)	0.56 (2.925)
Week 8 Change from Baseline(n=41,45,47,45)	-0.61 (1.517)	0.44 (1.694)	0.26 (1.775)	0.55 (2.786)
Week 12 Change from Baseline(n=39,44,46,45)	-0.79 (1.892)	0.49 (2.119)	0.31 (2.135)	0.41 (3.216)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4020
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 90%; -0.33 to 1.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8789
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 90%; -0.61 to 0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0345
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 90%; 0.19 to 1.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0087
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 90%; 0.48 to 2.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0268
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 90%; 0.28 to 1.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0047
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 90%; 0.58 to 2.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0116
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 90%; 0.38 to 1.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0220
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 90%; 0.27 to 1.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 90%; 0.62 to 2.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0067
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 90%; 0.56 to 2.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0225
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 90%; 0.33 to 2.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 90%; 0.55 to 2.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2391
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 90%; -0.12 to 0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9912
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.42 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 2. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1930
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 90%; -0.09 to 0.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation. (Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 90%; 0.35 to 1.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0394
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 90%; 0.12 to 1.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 4. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0862
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 90%; 0.02 to 0.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 90%; 0.48 to 1.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 90%; 0.37 to 1.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 8. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0132
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 90%; 0.29 to 1.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 30 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 90%; 0.65 to 2.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 60 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0115
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 90%; 0.40 to 1.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-06291874 100 mg
	Comments	Placebo was the reference and each of the active doses was the test for Week 12. The readings with residual greater than 3.5 times of its standard derivation were excluded from the presentation.(Excluding outliers)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0344
	Comments	Two (2)-sided p-values were from MMRM with baseline value, time (study day), treatment group, time by treatment interaction as fixed effects and an unstructured correlation matrix.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference from placebo
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 90%; 0.22 to 1.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments

Adverse Events

Time Frame	Baseline up to Day 119
Adverse Event Reporting Description	The same event might have appeared as both an AE and an SAE. However, what is presented are distinct events. An event might have been categorized as serious in 1 participant and as non-serious in another participant, or 1 participant might have experienced both a serious and non-serious event during the study.
Arm/Group Title	Placebo		PF-06291874 30 mg		PF-06291874 60 mg		PF-06291874 100 mg
Arm/Group Description	Four (4) tablets of placebo matched to PF-06291874 and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.		Two (2) placebo tablets, one 5-mg and one 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.		Two (2) 5-mg and two 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.		Four (4) 25-mg of PF-06291874 tablets and at least 1 stable dose of open label metformin were orally administered with a standard morning meal once daily for 12 weeks.
All Cause Mortality
	Placebo		PF-06291874 30 mg		PF-06291874 60 mg		PF-06291874 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PF-06291874 30 mg		PF-06291874 60 mg		PF-06291874 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		1/51 (2%)		0/52 (0%)		2/52 (3.8%)
Gastrointestinal disorders
Gastritis erosive	0/51 (0%)		0/51 (0%)		0/52 (0%)		1/52 (1.9%)
Hepatobiliary disorders
Cholecystitis acute	1/51 (2%)		0/51 (0%)		0/52 (0%)		0/52 (0%)
Infections and infestations
Abscess	0/51 (0%)		0/51 (0%)		0/52 (0%)		1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm benign	1/51 (2%)		0/51 (0%)		0/52 (0%)		0/52 (0%)
Psychiatric disorders
Adjustment disorder	0/51 (0%)		1/51 (2%)		0/52 (0%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		PF-06291874 30 mg		PF-06291874 60 mg		PF-06291874 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/51 (11.8%)		5/51 (9.8%)		2/52 (3.8%)		7/52 (13.5%)
Infections and infestations
Upper respiratory tract infection	3/51 (5.9%)		3/51 (5.9%)		0/52 (0%)		3/52 (5.8%)
Urinary tract infection	4/51 (7.8%)		2/51 (3.9%)		2/52 (3.8%)		4/52 (7.7%)

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.