Lilly's amylin drug eloralintide shows up to 20% weight loss in phase 2 trial

Eli Lilly's experimental once-weekly injection eloralintide helped adults with obesity or overweight lose between 9.5% and 20.1% of their body weight at 48 weeks, depending on dose, compared with 0.4% for placebo, the company reported on November 6, 2025 ^[1][3]. Lilly said it plans to begin enrolling phase 3 studies of eloralintide as a monotherapy for obesity by the end of the year ^[3].

Eloralintide is an amylin receptor agonist, meaning it works through a different hormone pathway than GLP-1 medicines such as Ozempic, Wegovy and Rybelsus (semaglutide) or Mounjaro and Zepbound (tirzepatide) ^[1]. Amylin analogs mimic a hormone released alongside insulin by the pancreas that suppresses appetite and reduces food intake ^[1]. Lilly designed eloralintide to be more selective for amylin receptors than for calcitonin receptors, based on the company's view that amylin activity, not calcitonin, drives weight loss ^[2].

What the trial found

The phase 2 study enrolled 263 adults across the U.S. with obesity or overweight plus at least one weight-related condition, and without type 2 diabetes. It was randomized, double-blind and placebo-controlled, and ran 48 weeks. Average starting weight was 109.1 kg, or about 240.5 pounds ^[3].

Mean weight change at 48 weeks, by trial arm ^[3]:

• 1 mg: -9.5% (-10.2 kg, about 22.5 lbs)
• 3 mg: -12.4% (-13.3 kg, about 29.3 lbs)
• 6 mg: -17.6% (-18.7 kg, about 41.2 lbs)
• 9 mg: -20.1% (-21.3 kg, about 47.0 lbs)
• 6 mg escalating to 9 mg: -19.9%
• 3 mg escalating to 6 mg then 9 mg: -16.4%
• Placebo: -0.4%

All treatment arms met the trial's primary endpoint of superior weight reduction versus placebo, using a measure that assumes all participants stayed on treatment ^[3]. Lilly also reported improvements in waist circumference, blood pressure, lipid profiles, blood sugar control and markers of inflammation, which were secondary endpoints and were not adjusted for multiple comparisons ^[3].

The most common side effects were mild to moderate gastrointestinal symptoms and fatigue. They appeared more often at higher doses and less often when doses were raised gradually; at the 1 mg and 3 mg doses, rates were similar to placebo ^[1][3]. Lilly has not yet released detailed side effect rates or how many patients stopped treatment ^[1]. In an earlier trial of eloralintide, "malaise" and "affective disorders" were reported, and Lilly has told analysts there is likely an association between the amylin class and feeling tired, which the company attributed to people eating less rather than to a psychiatric effect ^[2].

How it compares

No trial has compared eloralintide directly with semaglutide or tirzepatide, so its performance relative to approved drugs is not established. For context, Novo Nordisk's amylin candidate cagrilintide combined with the GLP-1 drug in Ozempic and Wegovy produced 20.4% or 22.7% weight loss at 68 weeks depending on which patients were included, while cagrilintide alone produced about 12%. Novo reported 22% weight loss at 36 weeks with amycretin, which acts on both GLP-1 and amylin receptors ^[2]. Cross-trial comparisons have limits because study designs, durations and patient groups differ.

"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," Kenneth Custer, president of Lilly Cardiometabolic Health, said in a statement. "We also are optimistic that it could be a complementary option for patients that need higher levels of efficacy" ^[2][3].

Why it matters for patients

Eloralintide is investigational. It is not approved by the Food and Drug Administration and is not available by prescription, and Lilly's own release notes there is no guarantee it will prove safe and effective or receive approval ^[3].

The practical interest is the mechanism. Some analysts and researchers say amylin drugs could be easier for patients to tolerate than GLP-1s and might help preserve lean muscle mass, though the phase 2 report did not include body-composition results ^[1]. How eloralintide's tolerability compares with approved options will depend on the full side effect and discontinuation data, which Lilly has not yet disclosed ^[1].

For people who cannot tolerate GLP-1 medicines or who do not get enough benefit from them, an amylin option could matter eventually — but only if later trials confirm the results and regulators clear it. Lilly is also studying eloralintide as an add-on to incretin therapy, a use that would not replace existing drugs ^[3].

What happens next

Phase 3 enrollment in obesity is scheduled to begin by the end of 2025, and Lilly said the phase 3 design details were not included in its release ^[2][3]. A separate phase 2 study (NCT06603571) is testing eloralintide alone and in combination with tirzepatide in adults with obesity or overweight and type 2 diabetes ^[3]. The phase 2 results were presented at ObesityWeek 2025 in Atlanta and published in The Lancet ^[3].