Lilly’s Oral GLP-1 Orforglipron Shows Superior Glycemic Control in Phase 3 Trials
Eli Lilly and Company has revealed promising results from its Phase 3 clinical trials for the oral GLP-1 receptor agonist, orforglipron. The trials, ACHIEVE-2 and ACHIEVE-5, demonstrate orforglipron’s superior glycemic control in adults with type 2 diabetes.
ACHIEVE-2 and ACHIEVE-5 Trial Highlights
In the ACHIEVE-2 trial, orforglipron achieved a significant reduction in A1C levels, lowering them by up to 1.7%. In comparison, the SGLT-2 inhibitor dapagliflozin only reduced A1C by 0.8%. Both medications were tested over a period of 40 weeks.
Meanwhile, the ACHIEVE-5 trial evaluated orforglipron’s effects when used alongside insulin glargine. Results showed that orforglipron lowered A1C by an impressive 2.1%, while the placebo group saw a reduction of only 0.8%.
Trial Details
- ACHIEVE-2: Compared orforglipron (3 mg, 12 mg, 36 mg) to dapagliflozin (10 mg) in 962 participants.
- ACHIEVE-5: Compared orforglipron (3 mg, 12 mg, 36 mg) to placebo in 546 participants.
Primary Endpoint Results
| Trial | Orforglipron Dose | A1C Reduction at 40 Weeks | Comparator | Comparator Reduction |
|---|---|---|---|---|
| ACHIEVE-2 | 3 mg | -1.7% | Dapagliflozin 10 mg | -0.8% |
| ACHIEVE-5 | 3 mg | -2.1% | Placebo | -0.8% |
Safety Profile
The safety and tolerability of orforglipron were consistent with previous studies. The most common adverse events were gastrointestinal in nature and typically mild to moderate. No significant hepatic safety signals were identified.
Future Plans
Lilly intends to submit orforglipron for regulatory approval for type 2 diabetes by 2026. Additionally, a submission for obesity treatment is scheduled for late 2025. The remaining trial, ACHIEVE-4, is expected to yield results in early 2026.
Understanding Orforglipron
Orforglipron is an investigational oral GLP-1 receptor agonist. This medication offers flexibility as it can be taken without dietary restrictions. Eli Lilly acquired the drug from Chugai Pharmaceutical Co., Ltd. in 2018.
Overall, the results from the ACHIEVE clinical trial program, involving over 6,000 participants, highlight orforglipron’s potential as a leading treatment option for type 2 diabetes and obesity.
