Background: PF-06882961 is an oral small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist with efficacy in nonclinical models comparable to injectable peptidic GLP-1R agonists. This randomized, double-blind, placebo-controlled, multiple ascending dose, Phase 1 study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics (PD) of PF–06882961 administered for 28 days in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 98 patients with T2DM taking metformin were randomized, in 8 cohorts (5 planned, 3 optional), to PF–06882961 (up to 120 mg twice daily [BID]) or placebo in a 3:1 ratio for 28 days, and 92 completed the inpatient study. Fasting plasma glucose (FPG), 24-hour mean daily glucose (MDG) and body weight were assessed at baseline and at Day 28.

Results: Multiple, oral doses of PF-06882961 were safe and well tolerated in adult participants with T2DM, and resulted in robust reductions in FPG, MDG and body weight at Day 28. The majority of adverse events (AEs) were mild, with AEs of nausea, dyspepsia, diarrhea, headache, constipation, and vomiting most commonly reported. There were no deaths and no serious AEs related to dosing of PF–06882961. No clinically significant adverse trends in labs, electrocardiogram or vital sign abnormalities were apparent.


A. Saxena: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. D. Gorman: Employee; Self; Pfizer Inc. K. Chidsey: None. C. Buckeridge: Employee; Self; Pfizer Inc. A.M. Kim: Employee; Self; Pfizer Inc. A. Bergman: Employee; Self; Pfizer Inc.

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