Phase 2 Trial Shows Promising Results
Eli Lilly reported that its experimental amylin agonist, eloralintide, achieved up to 20.1% weight loss after 48 weeks in a phase 2 trial. Based on these results, the company plans to begin phase 3 studies next month as it expands its presence in the obesity drug market.
In the mid-stage study, 263 adults who were overweight or had obesity with at least one related comorbidity, but without type 2 diabetes, received weekly injections of eloralintide or placebo. Patients on eloralintide experienced weight reductions ranging from 9.5% to 20.1%, compared to 0.4% with placebo.
Dose-Dependent Efficacy
The trial tested four dose levels, showing dose-dependent effects. Participants receiving the highest 9 mg dose lost the most weight, while those on escalating doses up to 9 mg achieved 16.4% and 19.9% reductions. At the lowest 1 mg dose, patients lost 9.5% of their body weight, equivalent to 10.2 kilograms, compared to 0.2 kilograms in the placebo group.
Safety and Tolerability
Lilly said the most common side effects were mild to moderate gastrointestinal symptoms and fatigue, which appeared more frequently at higher doses. The company noted that slower dose escalation reduced these effects. At the two lowest doses, with average weight loss of 9.5% and 12.4%, adverse event rates were similar to placebo. Earlier trials had observed “malaise” and “affective disorders,” though the company has said tiredness may relate to reduced food intake rather than psychiatric causes.
Mechanism and Market Comparison
Eloralintide is designed to selectively target amylin receptors over calcitonin receptors. According to Lilly, this selectivity supports the idea that amylin receptor agonism primarily drives weight loss, distinguishing the compound from other amylin-based drugs such as Novo Nordisk’s cagrilintide.
Novo’s cagrilintide, combined with GLP-1 medicines in Ozempic and Wegovy, achieved 20.4% to 22.7% weight loss after 68 weeks, while cagrilintide alone reached about 12%. Novo also reported 22% weight loss with its dual GLP-1 and amylin receptor agonist amycretin after 36 weeks.
Expert Commentary
Lilly’s president of Cardiometabolic Health, Kenneth Custer, Ph.D., said, “These data show that eloralintide, a selective amylin agonist, offers the potential for strong efficacy with improved tolerability and could serve as an alternative to incretin therapies.” He added that eloralintide may complement other treatments, such as GLP-1 receptor agonists, for patients seeking greater efficacy.
Analysts said the results demonstrate that amylin drugs can produce weight loss comparable to or greater than GLP-1 therapies. Jefferies analyst Lucy Codrington described the findings as the strongest evidence so far that the amylin class can deliver GLP-1-like or superior results. Kevin Gade, chief operating officer at Bahl and Gaynor, a Lilly shareholder, said the data positions Lilly as a leading player in the amylin drug category.
Market Impact
Following the announcement, shares of Zealand Pharma, Roche’s partner developing a competing amylin-based drug, fell 11%. Lilly’s upcoming phase 3 program will begin ahead of Zealand’s petrelintide, which is expected to deliver mid-stage results in the first half of next year. Analysts noted that while petrelintide may achieve 15–20% weight loss, comparisons will only be possible once full trial data become available.
Eli Lilly said it will provide additional details on the phase 3 trial design at a later stage.
