The amylin receptor agonist eloralintid – A new approach to the pharmacological treatment of obesity
Billings LK et al, Lancet. 2025;406(10520):2631-2643
In a placebo-controlled phase 2 study in patients with obesity, once-weekly subcutaneous administration of eloralintid over a period of 48 weeks resulted in weight loss of up to approx. 20%.
Background: Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. The authors 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.
Methods: The 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 body weight 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.
Findings: Between February 5, 2024, and August 14, 2025, 263 participants (mean age 49.0 years [SE 12.6], mean body weight 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%).
Interpretation: Eloralintide produced clinically meaningful, dose-dependent reductions in body weight over 48 weeks and was generally well tolerated, supporting eloralintide's potential use for obesity treatment.