Eli Lilly and Company reported positive topline results from its Phase 3 ATTAIN‑MAINTAIN study showing that orforglipron, a once‑daily oral glucagon‑like peptide‑1 (GLP‑1) receptor agonist, helped people maintain previously achieved weight loss after switching from injectable incretin therapies.
The trial followed adults with obesity or overweight who had completed up to 72 weeks of treatment with the highest tolerated doses of injectable GLP‑1 drugs — specifically Wegovy (semaglutide) or Zepbound (tirzepatide) — and had reached a weight‑loss plateau. Participants were re‑randomized to receive either orforglipron or placebo, alongside a healthy diet and physical activity, and were observed over 52 weeks. Orforglipron met the primary endpoint and all key secondary endpoints, delivering superior maintenance of body weight reduction compared with placebo.
In pre‑specified analyses at one year, participants who switched from Wegovy to orforglipron maintained their previous weight loss with an average difference of 0.9 kg versus placebo, while those who switched from Zepbound maintained their weight with an average difference of 5.0 kg. In post‑hoc analyses at 24 weeks — the last time point before placebo participants could receive rescue therapy — those switched from Wegovy to orforglipron had a mean weight change of −0.1 kg versus 9.4 kg for placebo, and those switched from Zepbound showed a mean change of 2.6 kg versus 9.1 kg for placebo.
The safety and tolerability profile was consistent with previous Phase 3 studies, with the most common adverse events being gastrointestinal and generally mild to moderate in severity; discontinuation rates due to adverse events were similar between orforglipron and placebo groups, and there were no hepatic safety signals.
Lilly has submitted orforglipron to the U.S. Food and Drug Administration for the treatment of adults with obesity or overweight.
