Eli Lilly and Company revealed topline results from its Attain-Maintain, Phase III clinical trial, evaluating orforglipron for weight maintenance over a 52-week period following initial treatment for 72 weeks with either the highest tolerated doses of Wegovy (semaglutide) or Zepbound (tirzepatide), in participants from Surmount-5 who were offered the opportunity to be re-randomized to receive orforglipron or placebo.¹

Orforglipron is an investigational, once-daily small molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist without restrictions on food and water intake and can be taken at any time throughout the day.¹

At the one-year mark, orforglipron reached the trial’s primary and all key secondary endpoints compared to placebo, displaying superior weight maintenance as an adjunct to a healthy diet and physical activity, employing the efficacy estimand and modified treatment-regimen estimand.¹

"Obesity is a chronic, progressive disease, and sustaining weight loss remains a significant challenge for many," said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. "Attain‑Maintain showed that orforglipron, a once-daily oral GLP-1, helped people maintain the weight they worked hard to lose. Participants in this study were able to switch directly from the highest tolerated doses of available injectable therapies onto oral doses of orforglipron. If approved for the treatment of obesity, orforglipron could provide a convenient alternative for the millions of individuals living with obesity around the globe to continue their long-term health journey."

Attain-Maintain was a 52-week, Phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of once-daily orforglipron compared to placebo for the maintenance of body weight reduction in adults with obesity or overweight with weight-related comorbidities who previously completed the Surmount-5 head-to-head trial. The Attain-Maintain trial randomized 376 participants across the U.S. into a three to two ratio to be administered either the maximum tolerated dose of orforglipron or placebo, as an adjunct to healthy diet and physical activity.¹

What were the results of the Attain-Maintain Phase III clinical trial?

Orforglipron met the trial’s primary endpoint of superior percent maintenance of body weight reduction compared to placebo among participants who previously reached a body weight plateau.¹ In pre-specified analyses at 52 weeks, participants who switched to orforglipron from Wegovy remained consistent with their previously achieved weight loss,averaging a difference of 2lbs., while those who switched to orforglipron from Zepbound maintained their previously achieved weight loss with an average difference of 11lbs., using the efficacy estimand.¹

In post-hoc analyses at 24 weeks, the final point before placebo participants were eligible for orforglipron as rescue therapy, the change in body weight from the study baseline for patients switching to orforglipron from Wegovy was -0.2 lbs. vs. 20.7lbs. for placebo. Likewise, for patients switching to orforglipron from Zepbound, the change from baseline was 5.7 lbs. vs. 20 lbs. for placebo.¹

Orforglipron’s overall safety and tolerability profile in Attain-Maintain was consistent with previous orforglipron Phase III studies, with the most common adverse events being gastrointestinal-related and generally mild-to-moderate in severity. No hepatic safety signal was observed.

Discontinuation rates because of adverse events for patients randomized to either placebo or orforglipron reached 4.8% for orforglipron from Wegovy, 7.6% for placebo from Wegovy, 7.2% for orforglipron from Zepbound, and 6.3% for placebo from Zepbound.¹

Sources

1. Lilly's orforglipron helped people maintain weight loss after switching from injectable incretins to oral GLP-1 therapy in first-of-its-kind Phase III trial Eli Lilly and Company December 18, 2025 https://www.prnewswire.com/news-releases/lillys-orforglipron-helped-people-maintain-weight-loss-after-switching-from-injectable-incretins-to-oral-glp-1-therapy-in-first-of-its-kind-phase-3-trial-302645471.html