Eli Lilly’s oral GLP-1 receptor agonist, orforglipron, has shown significant results in a Phase 3 clinical trial, raising expectations that a convenient oral alternative could disrupt the obesity treatment market, which has traditionally been dominated by injectables.
On Thursday, Eli Lilly announced topline results from the ACHIEVE-1 Phase 3 trial, reporting that orforglipron demonstrated statistically significant improvements in both glycated hemoglobin (A1C) and weight reduction compared to placebo over a 40-week treatment period. The study targeted adults with type 2 diabetes whose blood sugar levels were inadequately controlled with diet and exercise alone.
Orforglipron is the first oral GLP-1 receptor agonist that can be taken without restrictions on food or water intake. It is taken once daily and is being hailed as a potential replacement for existing injectable therapies.
According to the clinical trial results, orforglipron reduced baseline A1C levels of 8.0% by 1.3 to 1.6 percentage points, meeting its primary endpoint. In the highest dose group, over 65% of patients achieved A1C levels of 6.5% or lower, which meets the diagnostic criteria for diabetes control established by the American Diabetes Association (ADA).
The drug also showed a notable impact on weight loss. Patients in the highest dose group experienced an average weight reduction of 7.9%, with weight loss continuing through the end of the trial. This suggests that longer-term use of the drug could lead to even greater weight reduction.
David A. Ricks, Chairman and CEO of Eli Lilly, stated that Achieve-1 is the first of seven ongoing Phase 3 studies evaluating the safety and efficacy of orforglipron in patients with diabetes and obesity and that additional data is expected to be released in 2025.
Meanwhile, Eli Lilly plans to submit orforglipron for regulatory approval for weight management indications by the end of 2025, and aims to expand its use for type 2 diabetes treatment in 2026. Additionally, results from the ATTAIN Phase 3 program—focused specifically on evaluating orforglipron’s weight-loss effects—are also scheduled to be released later 2025.