Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.

Abstract

Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity. We enrolled 263 participants from 46 research centres in the USA. Individuals aged 18-75 years with a BMI of 30 kg/m² or higher, or a BMI of 27 kg/m² or higher with at least one weight-related comorbidity and without type 2 diabetes were randomly assigned (2:1:1:1:2:1:2) to receive once-per-week subcutaneous injections of placebo or eloralintide at 1 mg, 3 mg, 6 mg, or 9 mg, or dose escalations of 6-9 mg or 3-9 mg for 48 weeks. The primary endpoint was percent change in bodyweight from baseline after 48 weeks of treatment. Efficacy analyses included all randomly assigned participants, and safety analyses included all participants who were randomly assigned and received at least one dose of study treatment. This study was completed on Aug 14, 2025, and is registered with ClinicalTrials.gov (NCT06230523). Between Feb 5, 2024, and Aug 14, 2025, 263 participants (mean age 49·0 years [SE 12·6], mean bodyweight 109·1 kg [22·8], BMI 39·1 kg/m² [6·8], 204 [78%] female, and 205 [78%] White) were randomly assigned to receive eloralintide (1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6-9 mg, n=24; and 3-9 mg, n=52) or placebo (n=53). The efficacy analyses were based on the 263 participants randomly assigned. The mean percent change in bodyweight from baseline after 48 weeks (efficacy estimand) was -9% (1 mg, 95% CI -12·6 to -6·3), -12% (3 mg, -14·9 to -9·8), -18% (6 mg, -20·7 to -14·5), -20% (9 mg, -22·7 to -17·5), -20% (6-9 mg, -22·7 to -17·0), and -16% (3-9 mg, -18·6 to -14·1), compared with -0·4% (-2·2 to 1·4) in the placebo group. The most common adverse events with eloralintide were nausea (1 mg 11%, 3 mg 13%, 6 mg 64%, 9 mg 33%, 6-9 mg 54%, 3-9 mg 25%, and placebo 14%) and fatigue (1 mg 0%, 3 mg 13%, 6 mg 29%, 9 mg 43%, 6-9 mg 46%, 3-9 mg 21%, and placebo 12%). 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. Eli Lilly.