Eli Lilly’s Oral GLP-1 Drug Orforglipron Shows Strong Results In Phase III For Type 2 Diabetes

Chugai Pharmaceutical Co., Ltd. has announced that Eli Lilly and Company released positive topline results from the Phase 3 ACHIEVE-1 clinical trial, evaluating the safety and efficacy of orforglipron—an oral glucagon-like peptide-1 (GLP-1) receptor agonist—in adults with type 2 diabetes inadequately controlled with diet and exercise. This is the first Phase 3 study from the ACHIEVE program, including 559 participants.

Orforglipron successfully met its primary endpoint in the 40-week trial, demonstrating superior glycemic control versus placebo. According to the efficacy estimand approach, participants taking orforglipron achieved reductions in HbA1c levels ranging from 1.3% to 1.6% from a baseline of 8.0%. Additionally, in a key secondary endpoint, more than 65% of patients receiving the highest dose of orforglipron reached an HbA1c level of 6.5% or lower—meeting the threshold defined by the American Diabetes Association for diabetes diagnosis.

Beyond glycemic control, the treatment also positively impacted weight management. Patients on the highest dose of orforglipron lost an average of 16 pounds, representing 7.9% of their baseline body weight. The safety profile of orforglipron was in line with other agents in the GLP-1 class. 

The most frequently reported adverse events were gastrointestinal in nature, including diarrhoea, nausea, dyspepsia, constipation, and vomiting. These were generally mild to moderate in severity. Discontinuation rates due to adverse events were reported at 6% (3 mg), 4% (12 mg), and 8% (36 mg) for orforglipron, compared to 1% for placebo. Importantly, no hepatic safety signals were observed during the trial.

The results from ACHIEVE-1 will be presented at the 85th Scientific Sessions of the American Diabetes Association and published in a peer-reviewed journal. Eli Lilly also plans to disclose additional data from the broader ACHIEVE Phase 3 program and the ATTAIN program, which is focused on weight management, later this year.

Regulatory submissions for orforglipron as a weight management treatment are expected by the end of 2025, with filings for type 2 diabetes treatment anticipated in 2026. Chugai confirmed that this announcement will not impact its consolidated financial results for the fiscal year ending December 2025.