Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies

• DOI: 10.2337/dc15-1643
• Publication Date: 2016-01-07T20:06:12Z
• Authors: Christof M. Kazda; Ying Ding; Ronan P. Kelly; Parag Garhyan; Chunxue Shi; Chay Ngee Lim; Haoda Fu; David E. Watson; Andrew J. Lewin; William H. Landsc...; Mark A. Deeg; David E. Moller; Thomas A. Hardy
• Keywords: Glucagon receptor

OBJECTIVE Type 2 diabetes pathophysiology is characterized by dysregulated glucagon secretion. LY2409021, a potent, selective small-molecule receptor antagonist that lowers glucose was evaluated for efficacy and safety in patients with type diabetes. RESEARCH DESIGN AND METHODS The (HbA1c glucose) (serum aminotransferase) of once-daily oral administration LY2409021 assessed two double-blind studies. Phase 2a study were randomized to 10, 30, or 60 mg placebo 12 weeks. 2b 2.5, 20 24 RESULTS produced reductions HbA1c significantly different from over both After weeks, least squares (LS) mean change baseline –0.83% (10 mg), –0.65% (30 –0.66% (60 mg) (all P < 0.05) vs. placebo, 0.11%. LS –0.45% (2.5 –0.78% mg, 0.05), –0.92% (20 –0.15% placebo. Increases serum aminotransferase, fasting glucagon, total glucagon-like peptide-1 (GLP-1) observed; levels returned after drug washout. Fasting also lowered at doses associated only modest increases aminotransferases (mean increase alanine aminotransferase [ALT] ≤10 units/L). incidence hypoglycemia the groups not statistically CONCLUSIONS In diabetes, treatment good overall tolerability low risk hypoglycemia. Modest, reversible observed.