Lilly's Foundayo (orforglipron) outperforms oral semaglutide, dapagliflozin and placebo in ACHIEVE trials
- Foundayo 17.2 mg reduced A1C by 2.2% at 52 weeks versus 1.4% with oral semaglutide 14 mg, a 57.1% greater relative A1C reduction at the highest‑dose comparison.
- Foundayo 17.2 mg produced a mean 9.2% weight loss (19.7 lbs) versus 5.3% (11.0 lbs) with oral semaglutide 14 mg, a 73.6% greater relative weight loss at the highest‑dose comparison.
- In ACHIEVE‑2 and ACHIEVE‑5, up to 68.6% and 69.1% of participants on Foundayo achieved A1C ≤6.5%, versus 21.6% with dapagliflozin and 11.1% with placebo, respectively.
- Lilly plans to submit Foundayo for type 2 diabetes to the U.S. FDA by the end of Q2 2026 under the Commissioner's National Priority Review Voucher.
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.
Source: Lilly
