Eli Lilly’s Eloralintide Phase 2 Trial shows up to 20% Weight Loss with Promising Tolerability in Adults with Obesity

Eli Lilly recently announced encouraging results from a Phase 2 clinical trial evaluating eloralintide, a selective amylin receptor agonist, as a novel treatment for adults with obesity or overweight. The 48-week randomized, placebo-controlled trial demonstrated meaningful and dose-dependent weight loss, with reductions ranging from 9.5% to 20.1% at the highest dose, alongside favorable safety. These findings underscore eloralintide potential as a distinct therapeutic mechanism for obesity management, expanding options beyond current incretin-based drugs.

Study Design

The Phase 2 trial (NCT06230523) was a multicenter, double-blind, randomized; placebo-controlled study enrolling 263 adults aged 18 to 75 years with obesity or overweight plus at least one obesity-related comorbidity excluding those with type 2 diabetes. Participants were randomized to receive once-weekly subcutaneous injections of eloralintide at doses of 1 mg, 3 mg, 6 mg, or 9 mg, or dose escalation regimens of 3–9 mg or 6–9 mg, or placebo. The primary endpoint was percentage change in body weight from baseline at 48 weeks.

Results and Endpoints

At 48 weeks, all eloralintide treatment arms significantly outperformed placebo, which showed only a 0.4% mean weight reduction. Weight loss at the highest dose (9 mg) reached up to 20.1%, with other doses showing dose-dependent responses (9.5% to 20%). Secondary endpoints also improved significantly, including body mass index reduction and favorable changes in cardiometabolic risk factors such as waist circumference, blood pressure, lipid profiles, glycemic control, and markers of inflammation.

Safety and Tolerability

Eloralintide was generally well tolerated. The most common adverse events were mild to moderate gastrointestinal symptoms (notably nausea) and fatigue. These were dose-related and less frequent with slower dose escalations. Lower dose arms (1 mg and 3 mg) had adverse event rates similar to placebo, supporting a favorable safety profile.

About Amylin

Amylin, a hormone co-secreted with insulin by pancreatic beta cells, regulates appetite and gastric emptying. Amylin receptor agonists represent an emerging class of obesity treatments distinct from glucagon-like peptide-1 (GLP-1) receptor agonists, with the potential for complementary or alternative therapeutic options for weight management.

About Eloralintide

Eloralintide (development code LY3841136) is Eli Lilly’s once-weekly, long-acting, selective amylin receptor agonist being developed for chronic weight management, now advancing from Phase 2 to planned Phase 3 trial. Eloralintide was engineered as a potent, long-acting analog of human amylin with high selectivity for the amylin receptor, especially AMY1R, to drive satiety and reduce energy intake while aiming to mitigate nausea seen with less selective ligands. Eloralintide demonstrated preferential activation of human AMY1R over calcitonin receptor (CTR) and AMY3R in vitro and produced less conditioned taste avoidance than the nonselective comparator cagrilintide in rat studies, suggesting improved GI tolerability potential.

Amylin receptors (AMYR), especially AMY1R is particularly implicated in satiety signaling in the hindbrain and hypothalamus. Eloralintide selectively and potently activates AMY1R with much lower activity at CTR and reduced activity at AMY3R, consistent with focused amylin-pathway agonism enhance satiety and reduced caloric intake. Enhances satiety, reduces energy intake, slows gastric emptying are subsequently supports weight loss; Lilly communications emphasize decreased caloric intake mediated by satiety as the likely primary driver.