Eloralintide-Long-Acting Amylin Receptor Agonist Shows Significant Weight Loss in Obesity in a Phase 2 Trial
USA: A phase II randomized trial has found that subcutaneous injections of an investigational, selective long-acting amylin receptor agonist, Eloralintide, produced clinically meaningful reductions in body weight among adults with obesity.
Published in The Lancet, the study, led by Dr. Liana K Billings from Endeavor Health (NorthShore Hospitals), Skokie, Illinois, USA, and her team, assessed the safety and efficacy of Eloralintide administered once weekly over 48 weeks. The results highlight the potential of this new amylin-based therapy as a promising treatment option for individuals struggling with obesity.
Amylin receptor agonists are gaining attention as a new class of anti-obesity drugs. Eloralintide, a novel and selective long-acting compound, was evaluated for its ability to promote weight loss in adults who were either obese (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity but without type 2 diabetes.
The phase 2, multicentre, double-blind, randomised, placebo-controlled trial enrolled 263 participants from 46 research centres across the United States. Participants aged 18-75 years were randomly assigned to receive weekly subcutaneous injections of Eloralintide at doses of 1 mg, 3 mg, 6 mg, or 9 mg, or to dose-escalation regimens of 3–9 mg or 6–9 mg, or placebo. The primary outcome was the percentage change in body weight from baseline after 48 weeks of treatment.
The key findings were as follows:
- Eloralintide produced significant, dose-dependent reductions in body weight compared with placebo.
- Participants receiving 1 mg, 3 mg, 6 mg, and 9 mg doses of Eloralintide experienced mean weight losses of 9%, 12%, 18%, and 20%, respectively.
- Those on the 6–9 mg and 3–9 mg dose escalation regimens achieved 20% and 16% reductions in body weight, respectively.
- The placebo group showed only a minimal 0.4% decrease in body weight over the same 48-week period.
- The study participants had a mean age of 49 years, an average baseline weight of 109 kg, and a mean BMI of 39.1 kg/m².
- Approximately 78% of the participants were women, and most were White.
- Eloralintide was generally well tolerated, with nausea and fatigue being the most frequently reported adverse events.
- The incidence of nausea ranged from 11% to 64% across treatment groups.
- Fatigue occurred in 0% to 46% of participants, depending on the dosage.
- Most side effects were mild to moderate in severity and manageable, aligning with the expected profile of amylin-based therapies.
The authors concluded that Eloralintide led to clinically meaningful and sustained weight reduction over 48 weeks, demonstrating its potential as a novel therapeutic option for obesity management. The findings support further evaluation of Eloralintide in larger, long-term clinical trials to confirm its efficacy and safety profile.
Reference:
Billings, L. K., Hsia, S., Bays, H., Tidemann-Miller, B., O’Hagan, J., Tham, L. S., Butler, A., Kazda, C., Mather, K. J., & Coskun, T. (2025). Eloralintide, a selective amylin receptor agonist for the treatment of obesity: A 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. The Lancet. https://doi.org/10.1016/S0140-6736(25)02155-5
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