Orforglipron Outperforms Oral Semaglutide in Phase 3 ACHIEVE-3 Trial
Eli Lilly's oral orforglipron demonstrated superior HbA1c reduction and weight loss vs oral semaglutide in Phase 3, strengthening the case ahead of an April FDA decision.
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Eli Lilly is the dominant player in incretin obesity and diabetes care. Tirzepatide — Mounjaro for type-2 diabetes, Zepbound for obesity — generated the bulk of 2025 growth, and SURMOUNT-5, the first definitive Phase 3B head-to-head against semaglutide, read out 21.6% mean weight loss at 72 weeks versus semaglutide's 15.4%. Q1 2026 revenue reached $19.8 billion (+56% YoY) on Mounjaro $8.66B (+125%) and Zepbound $4.16B (+80%); Lilly raised 2026 guidance to $82–85B on April 30 and the stock climbed 6.11% on May 1. On May 4, an FAERS hepatic-failure case for Foundayo surfaced, sending shares down 3% premarket before recovering on Lilly's safety-data response and an RBC 'baseline noise' defense.
The next layer determines 2027 and beyond. Orforglipron, marketed as Foundayo, became the first small-molecule oral GLP-1 cleared for obesity in April 2026 and reached roughly 20,000 patients and more than 8,000 prescribers in its first three weeks, though Wegovy pill outpaced it ~20× in early-May IQVIA volume. Retatrutide, the GLP-1/GIP/glucagon triple agonist, posted its first Phase 3 type-2 diabetes readout (TRANSCEND T2D1: A1c down 1.7–2.0 pts, 25–37 lb mean weight loss) on the April 30 call alongside the prior TRIUMPH-4 obesity-with-knee-osteoarthritis data. The retatrutide MASLD Phase 3 (NCT06859268) is enrolling, building on 86% Phase 2 liver-fat reduction. LillyDirect handles self-pay distribution.
The company has spent 2024 and 2025 building peptide CDMO capacity to support both branded volume and the long shadow of the compounding fight. Stories here track the pipeline, deals, and the share-price moves that follow them.
Eli Lilly's oral orforglipron demonstrated superior HbA1c reduction and weight loss vs oral semaglutide in Phase 3, strengthening the case ahead of an April FDA decision.
Eli Lilly's triple-agonist achieved record weight loss at the highest dose with substantial reductions in knee osteoarthritis pain. Seven more Phase 3 trials expected in 2026.
Analysis of the TRIUMPH program (TRIUMPH-1 through TRIUMPH-4) published in Diabetes, Obesity, and Metabolism shows unprecedented average weight reduction of up to 24% across 5,800+ adults.