Oral GLP-1 Hits Phase 3 Trial Targets; Regulatory Submissions Coming

Eli Lilly and Company announced positive topline results from its Phase 3 ATTAIN-2 trial, showing that its investigational oral GLP-1 receptor agonist, orforglipron, achieved significant weight loss and improved cardiometabolic outcomes in adults with obesity or overweight status and type 2 diabetes.

The 72-week study evaluated three daily doses of orforglipron and met all primary and key secondary endpoints, according to a press release. Participants on the highest dose lost an average of 22.9 lb (10.5%) compared to 5.1 lb (2.2%) with placebo. Additionally, orforglipron lowered A1C by 1.3% to 1.8% across doses, with 75% of participants on the highest dose achieving an A1C ≤6.5%.

“The ATTAIN-2 results reinforce the potential for orforglipron, as a once-daily oral, to deliver meaningful weight loss and A1C reduction, consistent with similar landmark trials for injectable GLP-1s,” Lilly executive vice president and president of Lilly Cardiometabolic Health Kenneth Custer, PhD, said.“With these positive data in hand, we are moving with urgency toward global regulatory submissions to potentially meet the needs of patients who are waiting. If approved, we are ready to offer a convenient, once-daily pill that can be scaled globally—removing barriers and redefining how obesity is treated around the world.”

Lilly plans to move forward with global regulatory submissions for orforglipron later this year. The drug’s safety profile was consistent with other GLP-1 therapies and the most reported side effects were gastrointestinal-related and generally mild-to-moderate in severity. 

The company will present detailed ATTAIN-2 results at a future medical meeting and it is expected to be published in a peer-reviewed journal.