Lilly's amylin drug eloralintide reports about 20.1% weight loss in Phase 2

Eli Lilly said on November 6 that eloralintide, an investigational once-weekly injection that works through amylin receptors rather than GLP-1, produced average weight reductions of 9.5% to 20.1% after 48 weeks in a mid-stage trial of 263 adults with obesity or overweight ^[1]. The company said it will begin enrolling Phase 3 obesity studies next month ^[1].

The Phase 2 study (NCT06230523) was randomized, double-blind and placebo-controlled, and enrolled U.S. adults with obesity or overweight plus at least one weight-related condition, and without type 2 diabetes ^[1]. Participants were assigned to placebo; fixed doses of 1 mg, 3 mg, 6 mg or 9 mg; or one of two gradual dose-escalation schedules (6/9 mg or 3/6/9 mg) ^[1]. Average starting weight was 109.1 kg (240.5 lbs) ^[1].

What the numbers showed

Using what Lilly calls the efficacy estimand — an analysis that estimates results as if everyone had stayed on treatment for the full 48 weeks — average weight change was 9.5% (10.2 kg, 22.5 lbs) at 1 mg, 12.4% (13.3 kg, 29.3 lbs) at 3 mg, 17.6% (18.7 kg, 41.2 lbs) at 6 mg and 20.1% (21.3 kg, 47.0 lbs) at 9 mg ^[1]. The 6/9 mg escalation arm reached 19.9% and the slower 3/6/9 mg arm 16.4% ^[1]. Placebo was 0.4%, or about 0.2 kg ^[1]. Lilly notes these endpoints were not adjusted for multiplicity, a statistical caveat that means the individual dose comparisons should be read cautiously ^[1].

All treatment arms beat placebo on the primary endpoint, and Lilly also reported improvements in body mass index, waist circumference, blood pressure, lipids, glycemic control and inflammation markers ^[1]. Results were presented at ObesityWeek 2025 and published simultaneously in The Lancet ^[1].

On side effects, Lilly said the most common adverse events were mild to moderate gastrointestinal symptoms and fatigue, which occurred more often at higher doses ^[1]. The company said those events were less frequent with slower dose escalation and were similar to placebo in the 1 mg and 3 mg arms ^[1]. The press release does not give specific rates of nausea, vomiting or treatment discontinuation, so how eloralintide's tolerability compares numerically to GLP-1 drugs is not yet clear from these sources.

Amylin is a pancreatic hormone that slows digestion and suppresses hunger ^[2]. Eloralintide activates amylin receptors in the brain and slows gastric emptying, a different route than semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound), which act on GLP-1 and, for tirzepatide, GIP ^[2]. Jefferies analyst Lucy Codrington said the data are the strongest evidence yet that amylin drugs can deliver GLP-1-like or better weight loss ^[2]. Shares of Zealand Pharma, which is developing the competing amylin drug petrelintide with Roche, fell 11% on the news ^[2].

Why it matters for patients

Most approved obesity medicines available now work on the GLP-1 pathway, and nausea, vomiting and other gut side effects are a common reason people stop taking them. A drug with a different mechanism could eventually widen the menu. Lilly's cardiometabolic president, Kenneth Custer, framed eloralintide as a possible "alternative to incretin therapies" and a potential add-on for people who need more weight loss ^[1]. Lead author Liana K. Billings, M.D., said no single treatment works for everyone and that different mechanisms let patients find the best balance of effectiveness and tolerability ^[1].

Several limits are worth keeping in mind. This was a Phase 2 trial in 263 people, not a large outcomes study, and it did not compare eloralintide head-to-head with semaglutide or tirzepatide ^[1][2]. The efficacy estimand assumes continued treatment, so real-world results including people who stop early would likely be lower ^[1]. Lilly's own release cautions there is no guarantee future results will match these, or that the drug will be approved ^[1]. Nothing here changes what is on the market today; eloralintide is investigational and not available by prescription.

What happens next

Lilly said it plans to begin Phase 3 enrollment of eloralintide as a standalone obesity treatment by the end of 2025, with Reuters reporting a start next month ^[1][2]. A separate Phase 2 study (NCT06603571) is testing eloralintide alone or combined with tirzepatide in adults with obesity or overweight and type 2 diabetes ^[1]. Mid-stage data for Zealand's petrelintide is expected in the first half of next year ^[2]. Neither source gives a projected filing or approval date, and the number and design of the planned Phase 3 trials are not specified in these sources.