Eli Lilly's New Diabetes Drug Outperforms Novo Nordisk's Oral Semaglutide in Phase 3 Trial

Eli Lilly announced positive results from its Phase 3 trial of its investigational diabetes drug, orforglipron. The trial showed that orforglipron improved blood sugar levels and led to weight loss, outperforming Novo Nordisk's oral semaglutide. Eli Lilly plans to submit the data to regulatory authorities for approval.

Eli Lilly and Company (LLY) has announced positive results from its Phase 3 trial of orforglipron, an investigational diabetes drug. The trial, known as ACHIEVE-3, evaluated the efficacy and safety of orforglipron compared to Novo Nordisk's oral semaglutide in adults with type 2 diabetes inadequately controlled with metformin.

The primary endpoint of the trial was to demonstrate that orforglipron is non-inferior in A1C reduction from baseline after 52 weeks compared to oral semaglutide. The results showed that orforglipron outperformed oral semaglutide, lowering A1C by an average of 1.9% and 2.2% for the 12 mg and 36 mg doses, respectively, compared to 1.1% and 1.4% for the 7 mg and 14 mg doses of oral semaglutide Lilly's oral GLP-1, orforglipron, superior to oral semaglutide in head-to-head trial^[2].

Additionally, orforglipron demonstrated superior weight loss compared to oral semaglutide. Participants taking the highest dose of orforglipron lost an average of 19.7 lbs (9.2%), compared to 11.0 lbs (5.3%) with oral semaglutide, a 73.6% relative improvement in weight loss Lilly's oral GLP-1, orforglipron, superior to oral semaglutide in head-to-head trial^[2].

The trial also showed clinically meaningful improvements across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure, and triglycerides. Furthermore, orforglipron reduced high-sensitivity C-reactive protein (hsCRP) levels, a marker of inflammation, by 47.7% Lilly's oral GLP-1, orforglipron, superior to oral semaglutide in head-to-head trial^[2].

The safety and tolerability of orforglipron were consistent with previous trials, with gastrointestinal-related adverse events being the most commonly reported and generally mild to moderate in severity. Treatment discontinuation rates due to adverse events were 8.7% and 9.7% for the 12 mg and 36 mg doses of orforglipron, respectively, compared to 4.5% and 4.9% for oral semaglutide Lilly's oral GLP-1, orforglipron, superior to oral semaglutide in head-to-head trial^[2].

Eli Lilly plans to submit orforglipron for the treatment of type 2 diabetes to global regulatory agencies in 2026. The detailed results of the ACHIEVE-3 trial will be presented at a future medical meeting and published in a peer-reviewed journal.