Eli Lilly’s once-daily oral GLP-1 receptor agonist, orforglipron, delivered promising Phase 3 outcomes in two major studies. In the ATTAIN-1 trial, adults with obesity or overweight (without diabetes) lost an average of 27.3 pounds (12.4%) at 72 weeks on the highest dose, alongside improvements in waist circumference, blood pressure, cholesterol, triglycerides, and inflammation markers.

In the ACHIEVE-3 trial, which directly compared orforglipron to oral semaglutide in people with type 2 diabetes, Lilly’s candidate proved superior. At 52 weeks, orforglipron reduced A1C by up to 2.2% versus 1.4% with semaglutide, and patients lost 19.7 lbs (9.2%) compared to 11.0 lbs (5.3%) with semaglutide. Nearly three times as many participants reached near-normal blood sugar with orforglipron.

The safety profile was consistent with the GLP-1 class, with gastrointestinal events as the most common side effects. Lilly expects to file for obesity approvals as early as 2026, with type 2 diabetes submissions to follow.

Sources

ATTAIN-1 Study in The New England Journal of Medicine
Lilly ATTAIN-1 Trial Press Release
Lilly ACHIEVE-3 Trial Press Release
HCP Live Story About ATTAIN-1 and ACHIEVE-3 Trials

Previous Orforglipron Coverage

Lilly Advances Orforglipron Toward Approval After Third Phase 3 Win
Lilly’s Oral GLP-1 Falls Short of Expectations, Boosting Novo Nordisk
Lilly’s Oral GLP-1 Pill Shows Strong Phase 3 Results as Novo Submits Rival for FDA Approval