https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02155-5/abstract
Eloralintide for Obesity — Phase 2 Trial (The Lancet, Nov 2025)
Background: Eloralintide is a novel, selective amylin receptor agonist developed by Eli Lilly for weight management, distinguished from other amylin drugs (like cagrilintide) by being highly selective for the amylin 1 receptor (AMY1R) rather than also hitting the calcitonin receptor, which may improve its safety/tolerability profile.
Study design: A 48-week, phase 2, randomized, double-blind, placebo-controlled trial in 263 adults with obesity/overweight (BMI ≥30, or ≥27 with a weight-related comorbidity) and without type 2 diabetes, across 46 US sites. Participants received once-weekly subcutaneous injections of placebo or eloralintide at 1, 3, 6, or 9 mg, or dose-escalation regimens up to 9 mg.
Key findings:
- All eloralintide doses met the primary endpoint of percent bodyweight change at 48 weeks.
- Mean bodyweight reduction ranged from –9% (1 mg) to –20% (9 mg), versus –0.4% with placebo.
- The 9 mg dose produced a maximum mean weight loss of –21.3 kg, with no clear plateau by week 48.
- Dose-escalation to 9 mg (starting at 3 mg) improved tolerability while still achieving substantial weight loss (–16.4%).
- Secondary benefits included improved lipid profiles, reduced C-reactive protein, lower blood pressure, and reduced pulse rate (notably, no heart-rate increase, unlike GLP-1 drugs).
- Most common side effects: nausea and fatigue, generally mild-to-moderate and reduced by gradual dose escalation.
- No deaths and no cases of pancreatitis or cholecystitis were reported.
Interpretation: Eloralintide produced clinically meaningful, dose-dependent weight loss with a generally favorable tolerability profile, supporting its potential as a new treatment option for obesity, either alone or alongside incretin-based therapies (like tirzepatide). Phase 3 trials are needed to confirm these findings in larger, more diverse populations.
