339-OR: Oral Small-Molecule GLP-1R Agonist Danuglipron Robustly Reduces Plasma Glucose and Body Weight after Eight Weeks in Japanese Adults with Type 2 Diabetes Mellitus

Abstract

Danuglipron is an oral small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist shown to reduce plasma glucose and body weight after 28 days of treatment in adults with type 2 diabetes mellitus (T2DM) . This randomized, double-blind (sponsor-open) , placebo-controlled, Phase 1 study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of danuglipron in Japanese patients with T2DM. A total of 37 patients with T2DM inadequately controlled on diet and exercise alone were randomized to twice-daily (BID) oral doses of placebo or multiple, ascending doses of danuglipron titrated to 40 mg, 80 mg, and 120 mg for 8 weeks. Multiple, oral doses of danuglipron were generally safe in Japanese participants with T2DM and resulted in approximate dose-proportional increases in exposure and significant reductions in fasting plasma glucose (FPG) , 24-hour mean daily glucose (MDG) , glycated hemoglobin (HbA1c) , and body weight (Table) . Most adverse events (AEs) were mild or moderate, with AEs of nausea, vomiting, abdominal discomfort, diarrhea, and headache reported most frequently. There were no deaths and no serious AEs related to dosing of danuglipron. No clinically significant adverse trends in labs, electrocardiogram, or vital sign abnormalities were apparent. Disclosure R.Ono: Employee; Pfizer Japan Inc. K.Furihata: Other Relationship; Eli Lilly and Company, Pfizer Japan Inc. Y.Ichikawa: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Japan Inc. Y.Nakazuru: Employee; Pfizer Japan Inc., Stock/Shareholder; Pfizer Inc. A.Bergman: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. D.N.Gorman: Employee; Pfizer Inc. A.R.Saxena: Employee; Pfizer Inc. Funding Sponsored by Pfizer Inc.