Retatrutide Phase 3 published in NEJM: -24% body weight at 48 weeks

Summary

The phase 3 trial of retatrutide (Eli Lilly), published May 17, 2026 in the New England Journal of Medicine, confirms superior efficacy over other GLP-1 agonists in a prespecified subgroup of 312 women with PCOS and BMI >= 27. Mean weight loss at 48 weeks reached 24.1% vs 21.3% for tirzepatide (Mounjaro) in the same cohort. Crucially for PCOS management: 68% of participants with irregular cycles at baseline showed cycle normalization at 24 weeks, vs 54% for tirzepatide. Metabolic markers (HOMA-IR, free testosterone, SHBG) improved comparably across treatments. The adverse event profile (nausea, vomiting) is slightly higher than tirzepatide but diminishes after 8 weeks of dose titration. Retatrutide is not yet approved in Europe or the US — an EMA marketing authorization application is expected late 2026. This publication firmly positions triple GLP-1/GIP/glucagon agonism as the next therapeutic frontier in PCOS metabolic management.