Eli Lilly reported that its Phase 3 ATTAIN‑MAINTAIN study met its primary endpoint, showing that patients who switched from the injectable weight‑loss drugs Wegovy (semaglutide) or Zepbound (tirzepatide) to the oral GLP‑1 receptor agonist orforglipron maintained the weight they had lost over a 52‑week period. The study enrolled participants who had completed 72 weeks of therapy at the highest tolerated doses of Wegovy or Zepbound and were then randomized to receive a once‑daily oral dose of orforglipron or placebo. At one year, the orforglipron group preserved an average of 0.9 kg of weight loss versus 9.4 kg lost with placebo when switching from Wegovy, and preserved 5.0 kg versus 9.1 kg when switching from Zepbound.
The trial began with a 12 mg daily dose of orforglipron, which was increased every four weeks until the maintenance dose of 36 mg was reached. Participants who received placebo experienced a significant rebound, losing an additional 9.4 kg after switching from Wegovy and 9.1 kg after switching from Zepbound. The safety profile was consistent with earlier studies, with only mild‑to‑moderate gastrointestinal events reported and no new safety signals.
Orforglipron’s performance highlights a potential advantage over other oral GLP‑1 candidates. Unlike Novo Nordisk’s oral semaglutide, which can be affected by a food effect, orforglipron’s pharmacokinetics are not impacted by meals, allowing for greater flexibility in dosing. The data also demonstrate that patients who have already achieved weight loss on injectable therapies can transition to a daily pill without significant loss of benefit, addressing a key patient preference for oral medication.
The results support Lilly’s strategy to offer a comprehensive obesity portfolio that includes both injectable and oral options. The company has already submitted a new drug application to the FDA and received a Commissioner's National Priority Voucher, which can expedite the review process. If approved, orforglipron could launch in 2026, expanding Lilly’s market share in the rapidly growing obesity treatment space and providing a convenient alternative for patients who prefer a pill over injections.
Eli Lilly’s Q3 2025 financials underscored the commercial momentum behind its obesity products. Revenue rose 54% year‑over‑year to $17.60 billion, driven by strong demand for Mounjone and Zepbound. The company raised its full‑year 2025 revenue guidance to $63 billion–$63.5 billion, reflecting confidence in continued growth from its cardiometabolic pipeline. The orforglipron data reinforce the company’s trajectory and add a new revenue stream that could further accelerate earnings growth.
Kenneth Custer, Ph.D., executive vice president and president of Lilly’s cardiometabolic health division, said the data “demonstrate that orforglipron can help people maintain the weight they have worked hard to lose, providing a convenient oral alternative for millions of patients worldwide.” Analysts noted that the positive topline could accelerate regulatory review and broaden Lilly’s obesity portfolio, potentially capturing patients who prefer oral therapy over injections.
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