Investigative Amylin Agonist Eloralintide Proves Superiority to Placebo in Weight Management

Eloralintide, a selective amylin agonist in development by Eli Lilly and Company, has demonstrated superior weight mean weight reductions compared to placebo among adult patients with overweight or obesity and ≥1 weight-related comorbidity.1

Recently, amylin-based therapies have begun to show promise as obesity medications. Eli Lilly is currently investigating eloralintide to fill this treatment gap; this phase 2 study was conducted to evaluate the drug’s efficacy and safety over a range of doses and dose escalation plans.2

“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,” Liana Billings, MD, director of clinical and genetics research in diabetes and cardiometabolic disease at Endeavor Health and lead study author, said in a statement. “These phase 2 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.”1

Eloralintide is a once-weekly selective amylin receptor agonist previously known as LY3841136. It has the capacity to decrease calorie intake, likely mediated by affecting satiety. Another phase 2 study is currently underway to evaluate eloralintide both alone and in combination with tirzepatide for weight management in adults with obesity or overweight and type 2 diabetes (T2D).1

This phase 2 trial enrolled patients from 46 US-based research centers. For inclusion, patients were required to be aged 18-75 years and have a body mass index (BMI) of ≥30 kg/m2, or a BMI of ≥27 kg/m2 with ≥1 weight-related comorbidity and without T2D. These patients were randomly assigned in a 2:1:1:1:2:1:2 ratio to receive once-weekly 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.2

The primary endpoint for the trial was the percentage change in body weight from baseline after 48 weeks. Efficacy analyses included all randomized participants, and safety analyses included all randomly assigned patients who received ≥1 dose of study treatment.2

A total of 263 patients were included, with a mean age of 49 years, a mean body weight of 109.1 kg, and a mean BMI of 39.1 kg/m2. These patients were then randomly assigned to either eloralintide (1 mg, n = 28; 3 mg, n = 24; 6 mg, n = 28; 9 mg, n = 54; 6 to 9 mg, n = 24; 3 to 9 mg, n = 52) or placebo (n = 53). Mean percent change in body weight from baseline 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 to 9 mg, -22.7 to -17), and -16% (3 to 9 mg, -18.6 to -14.1), compared with -0.4% (-2.2 to 1.4) in placebo.2

The most common adverse events reported during the trial were mild to moderate gastrointestinal symptoms, such as nausea, and fatigue. The incidence of these events were similar to placebo in the 1 mg and 3 mg arms, and were lower with slower dose escalation.1

“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,” Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a statement. “We also are optimistic that it could be a complementary option for patients [who] need higher levels of efficacy.”1

According to a press release, Eli Lilly and Company plans to launch phase 3 trial enrollment by the end of 2025.1

References

1. Eli Lilly and Company. Lilly’s selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity and overweight. November 6, 2025. Accessed November 6, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-selective-amylin-agonist-eloralintide-demonstrated

2. Billings LK, Hsia S, Bays H, et al. 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. Published online November 6, 2025. doi:10.1016/s0140-6736(25)02155-5