Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Retatrutide (LY3437943) is a triple agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon like peptide 1 (GLP-1), and glucagon (GCG) receptors. This phase 2, double blind, randomized, placebo-controlled trial evaluated its efficacy and safety in adults with obesity (BMI ≥30 or BMI 27<30 with weight related conditions). Participants received subcutaneous retatrutide (1 mg, 4 mg, 8 mg, or 12 mg) or placebo weekly for 48 weeks. The primary endpoint was percentage change in body weight at 24 weeks. Results showed dose-dependent weight reductions: 7.2% (1 mg), 12.9% (4 mg), 17.3% (8 mg), and 17.5% (12 mg) at 24 weeks, and 8.7%, 17.1%, 22.8%, and 24.2%, respectively, at 48 weeks, compared to 1.6% and 2.1% with placebo. Up to 93% of participants achieved ≥10% weight loss with higher doses. Common adverse events were gastrointestinal (nausea, diarrhea) and dose-dependent increases in heart rate. Retatrutide demonstrated significant efficacy for obesity treatment with a manageable safety profile.

Retatrutide (LY3437943) is a triple agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon like peptide 1 (GLP-1), and glucagon (GCG) receptors. This phase 2, double blind, randomized, placebo-controlled trial evaluated its efficacy and safety in adults with obesity (BMI ≥30 or BMI 27<30 with weight related conditions). Participants received subcutaneous retatrutide (1 mg, 4 mg, 8 mg, or 12 mg) or placebo weekly for 48 weeks. The primary endpoint was percentage change in body weight at 24 weeks. Results showed dose-dependent weight reductions: 7.2% (1 mg), 12.9% (4 mg), 17.3% (8 mg), and 17.5% (12 mg) at 24 weeks, and 8.7%, 17.1%, 22.8%, and 24.2%, respectively, at 48 weeks, compared to 1.6% and 2.1% with placebo. Up to 93% of participants achieved ≥10% weight loss with higher doses. Common adverse events were gastrointestinal (nausea, diarrhea) and dose-dependent increases in heart rate. Retatrutide demonstrated significant efficacy for obesity treatment with a manageable safety profile.