Eli Lilly and Company (NYSE:LLY) shares rose 1% on Wednesday after the drugmaker reported that its investigational oral GLP-1 treatment, orforglipron, delivered stronger outcomes than Novo Nordisk’s oral semaglutide in a direct Phase 3 comparison.
The 52-week ACHIEVE-3 study followed 1,698 adults with type 2 diabetes. Results showed orforglipron produced more significant reductions in blood sugar and body weight. At the highest doses, patients taking orforglipron saw their A1C drop by 2.2%, compared with a 1.4% reduction for those on semaglutide.
Weight loss was also greater with Lilly’s candidate. Participants on 36 mg of orforglipron shed an average of 19.7 pounds, or 9.2% of body weight, while those on 14 mg of semaglutide lost 11 pounds, or 5.3%—a 73.6% relative advantage for orforglipron.
The trial further found that 37.1% of patients receiving the highest orforglipron dose reached near-normal blood sugar levels (A1C below 5.7%), compared to only 12.5% in the highest semaglutide group.
“These results, combined with orforglipron’s once-daily oral dosing and broad scalability, reinforce its potential as a foundational treatment for type 2 diabetes,” said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health.
Safety findings aligned with prior studies, with most side effects being gastrointestinal and mild to moderate in severity. Discontinuation rates were slightly higher for orforglipron—8.7% at 12 mg and 9.7% at 36 mg—versus 4.5% and 4.9% for semaglutide at 7 mg and 14 mg, respectively.
Eli Lilly plans to file for regulatory approval of orforglipron as a treatment for type 2 diabetes in 2026.
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