Study Of Safety And Efficacy Of PF-04991532 In Subjects With Type 2 Diabetes Mellitus

• Placebo (Drug): Tablets (n=6), 0 mg, once daily for 84 days
• 150 mg PF-04991532 (Drug): Tablets (n=1), 150 mg + tablets (n=5), 0 mg, all once daily for 84 days
• 450 mg PF-04991532 (Drug): Tablets (n=3), 150 mg + tablets (n=3), 0 mg, all once daily for 84 days
• 750 mg PF-04991532 (Drug): Tablets (n=5), 150 mg + tablets (n=1), 0 mg, all once daily for 84 days
• Sitagliptin 100 mg (Drug): Tablets (n=1), 100 mg strength + tablets (n=5), 0 mg, all once daily for 84 days

Primary outcomes

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 [Baseline, Week 12]: HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4 percent (%) and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.

Secondary outcomes

• Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12 [Baseline, Week 1, 2, 4, 8, 12]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8 [Baseline, Week 1, 2, 4, 8]: HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
• Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels [Week 12]: HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
• Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12 [Baseline, Week 1, 2, 4, 8, 12]: Overweight or obesity increases the risk for developing diabetes. The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c.
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Body Weight Gain From Baseline [Week 12]: Overweight or obesity increases the risk for developing diabetes. Participants with >= 1% or >= 2% body weight gain from baseline signifies a higher risk of diabetes.
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Body Weight Loss From Baseline [Week 12]: The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c. Participants with >= 1% or >= 2% body weight loss from baseline signifies an improvement of glycemia.

Sex: All, ages: 18 Years to 70 Years

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.

Participant flow

Outcome results

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 (Primary), Mean, percentage of hemoglobin: PF-04991532 150 mg 8.34 +/- 0.906; PF-04991532 450 mg 8.19 +/- 0.947; PF-04991532 750 mg 7.96 +/- 1.030; Sitagliptin 100 mg 7.97 +/- 1.086; Placebo 8.55 +/- 1.351 (p 0.6803)
• Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12 (Secondary), Mean, milligram/deciliter (mg/dL): PF-04991532 150 mg 172.68 +/- 39.612; PF-04991532 450 mg 169.16 +/- 41.703; PF-04991532 750 mg 159.11 +/- 44.878; Sitagliptin 100 mg 158.38 +/- 42.502; Placebo 183.61 +/- 57.517 (p 0.4757)
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8 (Secondary), Mean, percentage of hemoglobin: PF-04991532 150 mg -0.04 +/- 0.227; PF-04991532 450 mg -0.03 +/- 0.210; PF-04991532 750 mg -0.13 +/- 0.217; Sitagliptin 100 mg -0.07 +/- 0.200; Placebo -0.02 +/- 0.287 (p 0.2327)
• Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels (Secondary), Number, percentage of participants: PF-04991532 150 mg 4.5; PF-04991532 450 mg 9.1; PF-04991532 750 mg 23.3; Sitagliptin 100 mg 14.6; Placebo 11.6
• Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12 (Secondary), Mean, kilogram (kg): PF-04991532 150 mg 92.57 +/- 19.957; PF-04991532 450 mg 88.91 +/- 22.781; PF-04991532 750 mg 86.08 +/- 17.787; Sitagliptin 100 mg 87.48 +/- 19.883; Placebo 87.43 +/- 19.351 (p 0.2067)
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Body Weight Gain From Baseline (Secondary), Number, percentage of participants: PF-04991532 150 mg 17.78; PF-04991532 450 mg 18.18; PF-04991532 750 mg 15.56; Sitagliptin 100 mg 29.17; Placebo 23.26
• Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Body Weight Loss From Baseline (Secondary), Number, percentage of participants: PF-04991532 150 mg 55.56; PF-04991532 450 mg 47.73; PF-04991532 750 mg 46.67; Sitagliptin 100 mg 29.17; Placebo 41.86

Adverse events

Other adverse events by term

• Pfizer CT.gov Call Center, Study director, Pfizer