Global pharma giant Eli Lilly has said that its experimental once-daily oral obesity drug orforglipron successfully helped patients maintain weight loss in a late-stage clinical trial, marking a potential breakthrough for patients transitioning off injectable GLP-1 therapies.

 

The Phase 3 ATTAIN-MAINTAIN study tested orforglipron as a weight-maintenance therapy in people who had already lost weight after up to 72 weeks on the highest tolerated doses of Wegovy or Zepbound. Participants who had reached a weight-loss plateau were re-randomized to receive either orforglipron or a placebo and followed for 52 weeks.

 

At one year, the drug met its primary and all key secondary endpoints, delivering significantly better weight maintenance than placebo when combined with diet and physical activity, Lilly said.

 

"Obesity is a chronic, progressive disease, and sustaining weight loss remains a significant challenge for many," said Kenneth Custer, 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."

 

In pre-specified analyses at 52 weeks, patients who switched from Wegovy to orforglipron maintained their prior weight loss, with an average difference of 0.9 kilograms. Those transitioning from Zepbound maintained weight loss with an average difference of 5.0 kilograms, based on the efficacy estimand.

 

Post-hoc analyses at 24 weeks showed an even clearer divergence from placebo. Patients switching from Wegovy to orforglipron saw a 0.1-kilogram change from baseline, compared with a 9.4-kilogram gain in the placebo group. Among patients switching from Zepbound, weight change was 2.6 kilograms versus 9.1 kilograms for placebo.

 

Lilly said the safety profile of orforglipron was consistent with earlier Phase 3 studies. The most common side effects were gastrointestinal and generally mild to moderate. Discontinuation rates due to adverse events ranged from 4.8% to 7.6% across treatment and placebo groups, and no liver safety concerns were identified.