Eloralintide Phase 2 results published, moving Lilly beyond incretins

Eli Lilly said on Nov. 6, 2025, that its investigational once-weekly injection eloralintide produced average weight reductions of 9.5% to 20.1% after 48 weeks in a Phase 2 trial of 263 US adults with obesity or overweight, compared with 0.4% for placebo ^[1]. The results were presented at ObesityWeek 2025 and published at the same time in The Lancet ^[1][2].

Eloralintide is not an incretin drug. It is a selective amylin receptor agonist, previously known as LY3841136, and it is designed to reduce calorie intake through effects on satiety — the feeling of fullness ^[1]. That makes it a different mechanism from semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound), which act on GLP-1 and, in tirzepatide's case, GIP receptors.

What the trial measured

The study (NCT06230523) was a 48-week, randomized, double-blind, placebo-controlled trial in adults with obesity or overweight plus at least one weight-related health condition, and without type 2 diabetes ^[1]. Participants were assigned in a 2:1:1:1:2:1:2 ratio to placebo; 1 mg, 3 mg, 6 mg or 9 mg eloralintide; or one of two step-up schedules, 6/9 mg or 3/6/9 mg ^[1].

Average starting weight was 109.1 kg (240.5 lbs) ^[1]. Using what Lilly calls the efficacy estimand — which represents results as if everyone had stayed on treatment for the full 48 weeks — average weight change was: 1 mg, −9.5% (−22.5 lbs); 3 mg, −12.4% (−29.3 lbs); 6 mg, −17.6% (−41.2 lbs); 9 mg, −20.1% (−47.0 lbs); 6/9 mg escalation, −19.9% (−46.3 lbs); 3/6/9 mg escalation, −16.4% (−39.2 lbs); and placebo, −0.4% (−0.4 lbs) ^[1]. Lilly notes these endpoints were not adjusted for multiplicity, a statistical caveat that applies when several comparisons are made ^[1].

All doses also beat placebo on secondary endpoints of body weight and BMI reduction, and treatment was linked to improvements in waist circumference, blood pressure, lipids, blood sugar control and inflammation markers ^[1]. Specific numbers for those measures were not included in the company's announcement.

Side effects

The most common adverse events were mild to moderate gastrointestinal symptoms and fatigue, which occurred more often at higher doses ^[1]. Lilly said the rates were lower when the dose was raised more slowly, and were similar to placebo in the 1 mg and 3 mg groups ^[1]. The press release does not give dropout rates, rates of individual side effects such as nausea or vomiting, or serious adverse event counts; those details are in the full Lancet paper, which was not available in the sources reviewed here ^[2].

Why it matters for patients

Most approved obesity medicines available today are incretin-based, and gastrointestinal side effects are a common reason people stop taking them. An amylin drug is a different pathway, which is why Lilly frames eloralintide as a possible "alternative to incretin therapies" and a potential add-on "for patients that need higher levels of efficacy," in the words of Kenneth Custer, Ph.D., president of Lilly Cardiometabolic Health ^[1].

Study lead author Liana K. Billings, M.D., of Endeavor Health in Skokie, Illinois, said the data "suggest eloralintide could offer a promising tolerability profile without compromising on efficacy" ^[1].

Important limits: this was a mid-stage trial in 263 people, all in the US, and it excluded people with type 2 diabetes ^[1]. There was no head-to-head comparison against semaglutide or tirzepatide, so cross-trial comparisons of percentage weight loss are not apples-to-apples. Eloralintide is investigational and not approved by the FDA for any use. Pricing, availability and long-term safety are not yet known.

What happens next

Lilly said it plans to begin enrolling Phase 3 obesity studies of eloralintide as a monotherapy by the end of 2025 — the release, dated Nov. 6, says enrollment starts "next month" ^[1]. The company is also running a separate Phase 2 study (NCT06603571) testing eloralintide alone or combined with tirzepatide for weight management in adults with obesity or overweight and type 2 diabetes ^[1].

Lilly's own cautionary language notes there is no guarantee future study results will match results to date, or that eloralintide will be shown safe and effective or win regulatory approval ^[1]. Phase 3 programs in obesity typically take years, and no filing or approval timeline has been announced.