Lilly's Foundayo (orforglipron) outperforms oral semaglutide, dapagliflozin and placebo in ACHIEVE trials

Phase 3 head‑to‑head and active‑control results

The ACHIEVE program (ACHIEVE‑2, ‑3 and ‑5) evaluated oral orforglipron (Foundayo) in adults with type 2 diabetes. In ACHIEVE‑3 (52 weeks, head‑to‑head vs oral semaglutide), Foundayo 9 mg and 17.2 mg lowered A1C by 1.9% and 2.2% compared with 1.1% and 1.4% for oral semaglutide 7 mg and 14 mg; more patients on Foundayo 17.2 mg reached A1C <5.7% (37.1% vs 12.5%). Foundayo also produced greater mean weight loss (9 mg: 6.7%/14.6 lbs; 17.2 mg: 9.2%/19.7 lbs) versus oral semaglutide (7 mg: 3.7%/7.9 lbs; 14 mg: 5.3%/11.0 lbs).

Results vs dapagliflozin and placebo

In ACHIEVE‑2 (40 weeks, vs dapagliflozin on background metformin), Foundayo lowered A1C by up to 1.7% versus 0.8% with dapagliflozin, with up to 68.6% achieving A1C ≤6.5%; mean weight loss on Foundayo ranged from 7.1 to 15.0 lbs versus 6.0 lbs with dapagliflozin. In ACHIEVE‑5 (40 weeks, added to insulin glargine), Foundayo lowered A1C by up to 2.1% versus 0.8% with placebo, with up to 69.1% reaching A1C ≤6.5%; mean weight change on Foundayo ranged from a 4.9 lb loss to an 11.5 lb loss versus a 1.1 lb gain on placebo.

Safety, ancillary effects and regulatory timing

Across trials, the most common adverse events were gastrointestinal (nausea, diarrhea, vomiting, dyspepsia, decreased appetite). Discontinuation rates due to adverse events were higher on Foundayo versus comparators (ACHIEVE‑3: 8.7% and 9.7% for Foundayo 9 mg/17.2 mg vs 4.5%/4.9% for oral semaglutide; ACHIEVE‑2: 9.2%–12.4% vs 1.2% for dapagliflozin; ACHIEVE‑5: 3.6%–9.6% vs 3.6% for placebo). Foundayo showed clinically meaningful improvements in non‑HDL, HDL, VLDL, total cholesterol, systolic blood pressure and triglycerides. Lilly intends to submit Foundayo to the U.S. FDA for type 2 diabetes by the end of Q2 2026.