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

• Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 12 ] [ Designated as safety issue: No ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 8 ] [ Designated as safety issue: No ]
  HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
• Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes, and levels of 6.5% or higher indicate diabetes.
• Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 12 ] [ Designated as safety issue: No ]
  Overweight or obesity increases the risk for developing diabetes. The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c.
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Gain in Body Weight From Baseline [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  Overweight or obesity increases the risk for developing diabetes. Participants with >= 1% or >= 2% gain in body weight from baseline signifies a higher risk of diabetes.
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Loss in Body Weight From Baseline [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c. Participants with >= 1% or >= 2% loss in body weight from baseline signifies an improvement of glycemia.

• Change from baseline in fasting plasma glucose (mg/dL) [ Time Frame: Up to Day 84 ] [ Designated as safety issue: No ]
• Change from baseline in HbA1c [ Time Frame: Up to Day 84 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving HbA1c <7%, as well as the proportion achieving <6.5% [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
• Change from baseline in body weight [ Time Frame: Up to Day 84 ] [ Designated as safety issue: No ]
• Proportion of subjects with body weight gain from baseline ≥1%. [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
• Proportion of subjects with body weight loss from baseline ≥1%. [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
• Proportion of subjects with body weight gain from baseline ≥2% [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
• Proportion of subjects with body weight loss from baseline ≥2% [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
• As a measure of safety, patients will be monitored for SAEs and HAEs using a variety of tests and measures. [ Time Frame: Up to an average of 14 weeks ] [ Designated as safety issue: Yes ]
  Assessment of clinical laboratory tests, 12 lead ECGs, vital signs, adverse events (AEs), as well as serious AEs (SAEs), and including episodes of hypoglycemic adverse events (HAEs).

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

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

• Placebo Comparator: Placebo
  Placebo for PF-04991532 and sitagliptin
  Intervention: Drug: Placebo
• Experimental: 25 mg PF-04991532
  Intervention: Drug: 25 mg PF-04991532
• Experimental: 75 mg PF-04991532
  Intervention: Drug: 75 mg PF-04991532
• Experimental: 150 mg PF-04991532
  Intervention: Drug: 150 mg PF-04991532
• Experimental: 300 mg PF-04991532
  Intervention: Drug: 300 mg PF-04991532
• Active Comparator: Sitagliptin 100 mg
  Intervention: Drug: Sitagliptin 100 mg

Inclusion Criteria:

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

Exclusion Criteria:

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