Eli Lilly’s Phase II Trial of Eloralintide Shows Up to 20% Weight Reduction in Adults With Obesity

Eli Lilly has shared positive results from a Phase II clinical trial (NCT06230523) evaluating eloralintide, an investigational once-weekly, selective amylin receptor, in adults with obesity or overweight with at least one obesity-related comorbidity and without type 2 diabetes.¹

Through 48 weeks, all eloralintide treatment arms met the primary endpoint of percent change in bodyweight from baseline, demonstrating superior mean weight reductions. Further results from the study were presented at ObesityWeek 2025 and published in The Lancet.

Eloralintide Phase II results

According to the study authors, 263 participants (mean age 49.0 years, mean bodyweight 109.1 kg, BMI 39.1 kg/m², 78% female, 78% White) were randomized to receive either eloralintide (1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6-9 mg, n=24; 3-9 mg, n=52) or placebo (n=53) between Feb. 5, 2024, and Aug. 14, 2025.²

“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,” the authors wrote.

Emerging data from the Phase II trial show:

• After 48 weeks, mean percent change in bodyweight from baseline (efficacy estimand) ranged from -9% at 1 mg to -20% at 9 mg, compared with -0.4% in the placebo group.
• The greatest weight reductions were observed in the 9 mg and 6-9 mg cohorts (-20% each; 95% CI: -22.7 to -17.5 and -22.7 to -17.0, respectively).
• The most common adverse events were nausea and fatigue, occurring more frequently at higher doses, and were generally mild to moderate in severity.

In a press release, Liana K. Billings, MD, director of clinical and genetics research in diabetes and cardiometabolic disease at Endeavor Health, Skokie, Illinois, and lead author, said: "Obesity is a complex condition, and no single treatment works for everyone. To truly address each patient's needs, we need therapies with different mechanisms of action so that each person can receive the treatment that offers the best balance of effectiveness and tolerability for them. These Phase II data suggest eloralintide could offer a promising tolerability profile without compromising on efficacy, underscoring the potential of amylin receptor agonists to expand our therapeutic strategies and better serve individuals living with obesity."

Further Phase II research alongside tirzepatide

Lilly is also evaluating eloralintide alone or in combination with tirzepatide for weight management in adults with obesity or overweight and type 2 diabetes in a Phase II study (NCT06603571).³

• This Phase II trial is a parallel-group, double-blind, placebo-controlled study.
• It features nine treatment arms and one placebo arm.
• The primary endpoint is percent change from baseline in bodyweight at 48 weeks, with secondary measures including percentage of participants who achieve ≥5% bodyweight reduction, change from baseline in hemoglobin A1c (HbA1c), and pharmacokinetics.

In the press release, Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, added: "Lilly is advancing the most comprehensive pipeline of obesity medicines, with a commitment to deliver innovative treatments that reflect the diverse needs and preferences of people living with obesity. We believe that molecule specificity is important in this class. These data show that eloralintide, a selective amylin receptor agonist, offers the potential for strong efficacy with improved tolerability and could serve as an alternative to incretin therapies. We also are optimistic that it could be a complementary option for patients that need higher levels of efficacy. Based on the encouraging results from Phase II trials of eloralintide, we plan to begin Phase III enrollment by year-end."

References

1. Lilly's selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight. News release. Eli Lilly. November 6, 2025. Accessed November 6, 2025. https://www.prnewswire.com/news-releases/lillys-selective-amylin-agonist-eloralintide-demonstrated-meaningful-weight-loss-and-favorable-tolerability-in-a-phase-2-study-of-adults-with-obesity-or-overweight-302607061.html

2. Liana K Billings, Stanley Hsia, Harold Bays, Beth Tidemann-Miller, Jessica O’Hagan, Lai San Tham, Annabelle Butler, Christof Kazda, Kieren J Mather, Tamer Coskun. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicenter, double-blind, randomized, placebo-controlled trial. The Lancet, 2025. ISSN 0140-6736. https://doi.org/10.1016/S0140-6736(25)02155-5.

3. A Study to Investigate Weight Management With LY3841136 and Tirzepatide (LY3298176), Alone or in Combination, in Adult Participants With Obesity or Overweight With Type 2 Diabetes. ClinicalTrials.gov. Updated September 26, 2025. Accessed November 6, 2025. https://clinicaltrials.gov/study/NCT06603571