Eli Lilly's Orforglipron Shows 1.6% A1C Reduction in Phase III Trial

Eli Lilly and Company (LLY) announced on April 17 that its Phase III ACHIEVE-1 study for the oral small molecule GLP-1 receptor agonist, orforglipron, has achieved positive results. The study evaluated the safety and efficacy of orforglipron compared to a placebo in adults with type 2 diabetes who had inadequate glycemic control through diet and exercise alone. Orforglipron is the first oral small molecule GLP-1 receptor agonist to successfully complete Phase III trials, and it does not require any food or water restrictions upon administration.

The primary endpoint of the study was met, with orforglipron demonstrating a significant reduction in A1C levels at 40 weeks. The estimated treatment difference showed an average reduction in A1C from a baseline of 8.0% to between 1.3% and 1.6%. In a key secondary endpoint, over 65% of participants taking the highest dose of orforglipron achieved an A1C level of 6.5% or lower, which is below the threshold defined by the American Diabetes Association. Additionally, participants on the highest dose of orforglipron experienced an average weight loss of 16.0 pounds (7.9%).

The safety profile of orforglipron was consistent with the established GLP-1 class. The most commonly reported adverse events were gastrointestinal in nature, typically mild to moderate in severity. The most frequent adverse events in participants taking orforglipron (3 mg, 12 mg, and 36 mg) were diarrhea (19%, 21%, and 26% respectively), nausea (13%, 18%, and 16%), dyspepsia (10%, 20%, and 15%), constipation (8%, 17%, and 14%), and vomiting (5%, 7%, and 14%). The overall discontinuation rate due to adverse events was 6% (3 mg), 4% (12 mg), and 8% (36 mg), compared to 1% in the placebo group. No hepatic safety signals were observed.

The results of the ACHIEVE-1 study will be presented at the 85th Scientific Sessions of the American Diabetes Association and published in a peer-reviewed journal. Additional results from the ACHIEVE Phase III clinical trial program, as well as data from the ATTAIN Phase III clinical trial program evaluating orforglipron for weight management, are expected to be shared later this year. Eli Lilly plans to submit a marketing application for orforglipron for weight management to global regulatory authorities by the end of this year, with a submission for type 2 diabetes treatment expected in 2026.

David A. Ricks, Chairman and Chief Executive Officer of Eli Lilly, expressed his satisfaction with the results, stating that the ACHIEVE-1 study is the first of seven trials evaluating the safety and efficacy of orforglipron in patients with type 2 diabetes and obesity. He highlighted that orforglipron met the company's expectations for safety, tolerability, glycemic control, and weight loss. As a convenient once-daily pill, orforglipron could offer a new treatment option if approved, with the potential for easy and large-scale production and distribution globally.