Eloralintide posts up to 20% weight loss in phase 2 and heads to phase 3

Eli Lilly said on Nov. 6 that its experimental once-weekly injection eloralintide produced average weight loss of 9.5% to 20.1% at 48 weeks in a phase 2 trial, compared with 0.4% for placebo ^[3]. The company said it will begin enrolling phase 3 obesity studies by the end of 2025 ^[3]. The results were presented at ObesityWeek 2025 in Atlanta and published simultaneously in The Lancet ^[3].

Eloralintide is not a GLP-1 drug. It is a selective amylin receptor agonist, meaning it mimics amylin, a hormone released from the pancreas along with insulin that suppresses appetite and reduces food intake ^[1]. Lilly says the effects are likely driven by satiety, the feeling of fullness ^[3]. Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) work through different gut hormone pathways.

What the trial found

The study randomized 263 US adults with obesity, or overweight plus at least one weight-related condition, and excluded people with type 2 diabetes ^[3]. Average starting weight was 109.1 kg, or 240.5 pounds ^[3]. Participants got placebo or one of six eloralintide regimens over 48 weeks ^[3].

Results by group, using what Lilly calls the efficacy estimand — the result if everyone had stayed on treatment for the full 48 weeks ^[3]: 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); a two-step escalation to 6 then 9 mg, −19.9% (46.3 lbs); a three-step escalation of 3/6/9 mg, −16.4% (39.2 lbs); placebo, −0.4% ^[3]. Lilly also reported improvements in waist circumference, blood pressure, lipids, blood sugar control and inflammation markers ^[3]. The secondary endpoints were not adjusted for multiplicity, a statistical caveat Lilly flagged in its own table ^[3].

The most common side effects were mild to moderate gastrointestinal symptoms and fatigue, seen more often at higher doses ^[3]. Rates were lower when doses were raised more slowly, and were similar to placebo in the 1 mg and 3 mg groups ^[3]. Lilly has not yet released detailed side effect rates or how many people stopped treatment during the trial ^[1]. Fierce Biotech reported that "malaise" and "affective disorders" turned up in an earlier eloralintide study, and that Lilly told Guggenheim analysts the tiredness may reflect people eating less rather than a psychiatric effect ^[2].

How it compares

For context, Fierce Biotech notes that Novo Nordisk's amylin drug cagrilintide alone produced about 12% weight loss, while cagrilintide combined with semaglutide reached 20.4% or 22.7% at 68 weeks depending on the analysis, and Novo's dual GLP-1/amylin drug amycretin hit 22% at 36 weeks ^[2]. Those are separate trials with different lengths and patient groups, so the numbers are not directly comparable.

Eloralintide is designed to hit amylin receptors more selectively than calcitonin receptors, which Lilly says sets it apart from cagrilintide ^[2]. Some analysts and researchers believe amylin drugs may be easier to tolerate than GLP-1s and may help preserve lean muscle, though that has not been established in these results ^[1].

Why it matters for patients

The practical takeaway is that a non-GLP-1 mechanism reached weight loss numbers in the same range as injectable GLP-1 medicines in a mid-stage study — something that could eventually matter for people who cannot tolerate current drugs. Lilly executive Kenneth Custer said eloralintide "could serve as an alternative to incretin therapies" and might also be a "complementary option for patients that need higher levels of efficacy" ^[2][3].

But this is phase 2 data in 263 people over 48 weeks, not an approved product. Full safety details, dropout rates and long-term outcomes are not yet public ^[1]. Phase 2 results have not always held up in larger trials, a risk Lilly acknowledges in its own forward-looking statement ^[3]. There is no approval timeline, no price and no launch date yet.

What happens next

Lilly plans to start phase 3 enrollment for eloralintide as a standalone obesity treatment by the end of 2025 — CNBC reported it as beginning next month ^[1][3]. The company has not released the phase 3 trial design ^[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 ^[3]. Phase 3 obesity programs typically run for years, so approval, if it comes, is well down the road.