Orforglipron tops oral semaglutide
A head‑to‑head trial found orforglipron (an oral GLP‑1 candidate) delivered larger HbA1c and weight reductions than oral semaglutide — promising a needle‑free alternative for type‑2 diabetes care. (ajmc.com) The report frames orforglipron as a meaningful oral competitor in the incretin space. (ajmc.com)
ACHIEVE-3 was a randomized, open‑label Phase 3 trial that ran 52 weeks and enrolled 1,698 adults with type 2 diabetes, randomizing participants into four active arms: orforglipron 12 mg, orforglipron 36 mg, oral semaglutide 7 mg, and oral semaglutide 14 mg. (clinicaltrials.gov) Using the efficacy estimand at week 52, mean HbA1c declines were reported as −1.9% for orforglipron 12 mg and −2.2% for orforglipron 36 mg versus −1.1% for oral semaglutide 7 mg and −1.4% for oral semaglutide 14 mg. (prnewswire.com) For the key weight endpoint, Lilly reported mean loss of 19.7 lb (9.2%) with orforglipron 36 mg versus 11.0 lb (5.3%) with oral semaglutide 14 mg at 52 weeks, a 73.6% greater relative weight reduction for the higher orforglipron dose. (drugs.com) Investigators noted baseline mean HbA1c around 8.3% and said more participants on orforglipron achieved glycemic targets: roughly 72–76% reached HbA1c <7.0% on orforglipron versus about 54–64% on semaglutide, with separation appearing as early as week 4. (lilly.mediaroom.com) Safety signals showed higher discontinuation for adverse events in the orforglipron groups (≈9–10%) compared with semaglutide groups (≈4–5%), with gastrointestinal events reported as the most common reason for stopping treatment. (bmj.com) Lilly submitted orforglipron to regulators in more than 40 countries and cited a potential U.S. regulatory action for obesity in Q2 2026; the ACHIEVE-3 results were published in The Lancet on Feb 26, 2026. (lilly.mediaroom.com)
