NEJM publishes Phase 2 results of daily oral orforglipron in adults with obesity

Eli Lilly/Orforglipron (Foundayo)

NEJM published a Phase 2 trial of orforglipron, a once-daily GLP-1 small-molecule pill in 272 adults with obesity. Weight fell 8.6% to 12.6% at 26 weeks and 9.4% to 14.7% at 36 weeks depending on dose versus ~2% on placebo; 10-17% stopped due to GI side effects.

• Orforglipron is first nonpeptide oral GLP-1 agonist; avoids injectable burden and GLP-1 peptide immunogenicity risk.
• Dose range tested: 12–45 mg daily; dose-dependent efficacy and tolerability.
• Weight loss 9.4%–14.7% at 36 weeks on high dose rivals injectable GLP-1 (Wegovy ~15%).
• GI side effects (nausea, diarrhea) led 10–17% discontinuation; milder than some injectables at similar doses.