A novel, selective amylin receptor agonist, eloralintide, has demonstrated significant, dose-dependent weight loss in adults with obesity or overweight, according to the results of a 48-week phase 2 trial (NCT06230523).¹ Amylin-based therapies are an emerging class of promising medications for weight management.²

This multicentre, double-blind, randomised, placebo-controlled trial was conducted across 46 research centres in the USA. The study enrolled 263 participants aged 18–75 years with a Body Mass Index (BMI) of ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, and without type 2 diabetes.¹

Participants were randomly assigned to receive once-weekly subcutaneous injections of placebo or eloralintide for 48 weeks. The eloralintide arms included fixed doses of 1 mg, 3 mg, 6 mg, and 9 mg, as well as dose-escalation schemes of 6–9 mg and 3–9 mg. The primary endpoint was the percentage change in bodyweight from baseline to week 48.¹

At 48 weeks, participants receiving eloralintide achieved substantial reductions in bodyweight compared with those on placebo. The mean percent change from baseline was –0.4% in the placebo group.¹

In the treatment arms, the mean weight loss was dose-dependent: –9% for the 1 mg dose, –12% for the 3 mg dose, –18% for the 6 mg dose, and –20% for the 9 mg dose. The dose-escalation groups also showed significant reductions, with a –20% change for the 6–9 mg group and –16% for the 3–9 mg group.¹

The most frequently reported adverse events with eloralintide were nausea and fatigue. For the 9 mg dose, nausea was reported by 33% of participants and fatigue by 43%, compared with 14% and 12% in the placebo group, respectively.¹

The trial, led by Dr Liana Billings, concluded that eloralintide "produced clinically meaningful, dose-dependent reductions in bodyweight over 48 weeks and was generally well tolerated, supporting eloralintide's potential use for obesity treatment."¹ These findings suggest that selective amylin receptor agonism is a viable mechanism for achieving significant weight loss in individuals with obesity.

This study was funded by Eli Lilly.

References

1. Billings LK, Hsia S, Bays H, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2025. Published online November 6. https://doi.org/10.1016/S0140-6736(25)02155-5

2. Briere DA, Qu H, Lansu K, et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: from discovery to clinical proof of concept. Mol Metab. 2025. Published online Oct 16. https://doi.org/10.1016/j.molmet.2025.102271

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