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Eli Lilly reported mid-stage trial results showing a combination obesity regimen produced substantially greater weight loss than a high dose of its bestselling drug tirzepatide alone. The company said the mix of its experimental amylin-targeting compound with a lower dose of tirzepatide also improved blood-sugar control in people with obesity and Type 2 diabetes.
Stronger weight loss when three hormone pathways are targeted
In a 48-week Phase 2 study, participants receiving the highest-dose combination lost an average of 23.3% of their body weight — roughly 54 pounds — compared with 14.8% (about 34.4 pounds) for those on a 15-milligram dose of tirzepatide alone. Patients treated with the amylin drug by itself lost up to 12.3% of body weight, or about 28.6 pounds on average.
Mid-stage trial shows Eli Lilly combo delivers bigger weight loss, company says
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The experimental amylin agent, called eloralintide, was paired with low-dose tirzepatide, which acts on the gut hormones GLP-1 and GIP. Lilly says the rationale is to engage three nutrient‑responsive hormones — GLP‑1, GIP and amylin — to increase satiety and further reduce appetite.
The combo also produced larger reductions in average A1C, a key measure of long-term blood sugar. The company reported up to a 2.9% A1C drop with the combination, versus up to 2.4% for higher-dose tirzepatide alone and up to 1.4% for eloralintide as monotherapy.
Tolerability, dropouts and what to watch
Lilly acknowledged higher discontinuation rates with the combination regimen. Depending on dose, between 10.8% and 27% of participants stopped the combo treatment because of side effects, compared with 2.9% for the tirzepatide-only group in the trial.
Gastrointestinal symptoms were the most commonly reported adverse events. Lilly said these were generally mild to moderate and tended to occur during dose escalation.
Ken Custer, president of Lilly Cardiometabolic Health, cautioned that Phase 2 tolerability data do not always predict final dosing strategies. “It’s probably not the best indicator of the tolerability of a medicine,” he told CNBC, noting that mid‑stage trials are used to learn how best to administer a drug before later-stage studies. He added the company expects to refine dosing for Phase 3 to improve the balance of efficacy and tolerability.
Regulatory path and next development steps
Lilly said it intends to move the combination into Phase 3 testing. The company has described timelines that referenced starting Phase 3 at the end of the year and has also noted plans to advance the program into Phase 3 by the end of 2026 in presentations at the European Association for the Study of Diabetes in Milan.
The firm is also developing a co-formulation so patients could receive both agents in a single injection rather than separate shots.
How the results fit into the competitive landscape
Analysts and industry observers framed the findings as a potential rival to other next-generation obesity strategies that pair amylin and GLP‑1 activity. Before Lilly released the Phase 2 data, Leerink Partners analyst David Risinger said he sees “mega-blockbuster” potential for an amylin-targeting drug like eloralintide, pointing to millions of patients who either did not achieve desired results from existing GLP‑1 therapies or could not tolerate their side effects.
Lilly’s combination approach will now be evaluated alongside other multi-hormone candidates. One such comparator is Novo Nordisk’s investigational CagriSema, which also combines amylin and GLP‑1 mechanisms. Another Lilly program, retatrutide, targets GLP‑1, GIP and glucagon and has produced some of the largest weight-loss signals reported in clinical trials to date.
Evidence from earlier testing
The Phase 2 results build on earlier proof-of-concept work. Lilly reported that in a Phase 1 study, adding 3 milligrams of eloralintide to 5 milligrams of tirzepatide produced roughly 17% weight loss over 16 weeks, compared with about 10% with the same dose of tirzepatide alone.
Those preliminary data helped shape the larger mid-stage study and provided the basis for advancing the combination into longer, more definitive trials.
