By Fineline Cube 
Eli Lilly and Company (NYSE: LLY) announced positive topline results from the open‑label, randomized Phase 3 ACHIEVE‑3 study. The trial evaluated orforglipron, an oral GLP‑1 receptor agonist, against oral semaglutide in 1,698 adults with type 2 diabetes inadequately controlled with metformin.
Study Design
- Open‑label, head‑to‑head comparing orforglipron 12 mg & 36 mg vs. oral semaglutide 7 mg & 14 mg.
- 52‑week duration, approved‑label dosing for semaglutide and once‑daily dosing for orforglipron, no food or water restrictions.
- Primary endpoint: A1C reduction; secondary endpoints: A1C < 5.7 %, weight loss, and cardiovascular risk markers.
Key Results
| Outcome | Orforglipron 12 mg | Orforglipron 36 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg |
|---|---|---|---|---|
| Mean A1C ↓ | 1.9 % | 2.2 % | 1.1 % | 1.4 % |
| % achieving A1C < 5.7 % | – | 37.1 % | – | 12.5 % |
| Mean weight loss | 14.6 lb (6.7 %) | 19.7 lb (9.2 %) | 7.9 lb (3.7 %) | 11.0 lb (5.3 %) |
- Orforglipron met all primary and key secondary endpoints and delivered 73.6 % greater relative weight loss at the highest dose.
- Significant improvements were also seen in non‑HDL cholesterol, systolic BP, and triglycerides.
- The safety profile remained consistent with earlier trials, with no new safety signals.
Implications for Diabetes Therapy
- Orforglipron offers a once‑daily, food‑independent regimen that may enhance patient adherence.
- The superior glycemic and weight‑loss benefits position it as a compelling next‑step for patients failing metformin.
- Eli Lilly’s portfolio expansion into non‑peptide GLP‑1 agonists underscores its commitment to innovative diabetes solutions.-Fineline Info & Tech