Elie Lilly said Wednesday that its experimental combination regimen showed greater weight loss than a high dose of its top-selling drug, tirzepatide, alone in a mid-stage trial of patients with obesity and type 2 diabetes.
The combination therapy achieved the primary study objectives in a population that typically has difficulty losing weight. The results reinforce hope that it could serve as a successful alternative treatment option for people who have not responded or seen the results they wanted with GLP-1 products currently on the market. Lilly said it plans to start phase 3 trials on this diet at the end of the year.
The combination treatment combines Lilly’s investigational drug eloralintide, which targets amylin – a pancreatic hormone involved in appetite and satiety – with a low dose of tirzepatide, the active ingredient in its obesity injection Zepbound and its diabetes counterpart Mounjaro.
Tirzepatide targets two gut hormones, GLP-1 and GIP. Lilly believes that using all three pathways, including amylin, can further reduce appetite and improve weight loss – and that’s exactly what the combination drug did during the 48-week phase 2 trial.
People taking the highest dose of the combination diet lost up to 23.3 percent of their weight, or about 54 pounds, on average. This treatment combined 9 milligrams of amylin and 15 milligrams of tirzepatide.
Meanwhile, patients taking just a 15-milligram dose of tirzepatide saw a weight loss of 14.8 percent, or 34.4 pounds, on average. Those who took eloralintide alone lost an average of up to 12.3% of their weight, or 28.6 pounds.
“Patients may not get what they need from a drug like tirzepatide,” Ken Custer, president of Lilly Cardiometabolic Health, said in an interview. “They may not get what they need from a drug like eloralintide alone. The ability to combine them and achieve even greater weight loss – that’s certainly a” clear benefit of the new regimen.
Lilly signage during a groundbreaking ceremony for the Eli Lilly and Company pharmaceutical manufacturing campus at Generation Park in Houston, Texas, United States, Monday, September 21, 2026.
Marc Felix | Bloomberg | Getty Images
The combination treatment also reduced a key measure of blood sugar levels – A1C – by up to 2.9% on average. The higher-dose tirzepatide reduced A1C by up to 2.4% on average, while the amylin drug reduced it by up to 1.4% on average.
Lilly may face more questions from investors and the medical community about how patients tolerate and continue with this highly effective combination therapy.
More patients on the combination regimen – 10.8% to 27%, depending on dose – stopped treatment because of side effects, compared with 2.9% of people on tirzepatide alone in the trial.
Up to 10.8% of people taking only the drug amylin stopped treatment due to side effects, compared to 16.7% with the placebo.
Lilly said side effects were more common in groups taking the combination regimen compared to tirzepatide or the amylin drug alone. The most common side effects of the combination therapy were gastrointestinal, usually mild or moderate, and occurred primarily when patients increased doses during the trial.
But Custer cautioned against reading too much into the combination regimen’s discontinuation rates during Phase 2. He noted that the highest dose of tirzepatide also showed high rates, around 25%, in a mid-stage trial in 2018.
“It’s probably not the best indicator of a drug’s tolerability,” Custer told CNBC. “We do things in phase 1 and phase 2 to test what the molecule can do from an efficacy standpoint. We also learn from these studies about how we should administer them, and then we make changes. We do that every time.”
Lilly plans to adjust the combination treatment’s dosing regimens in phase 3 trials, “and we hope we get a very favorable balance between efficacy and tolerability,” Custer added.
Lilly also plans to develop a co-formulation of the two drugs in phase 3 trials, meaning patients will only need a single injection of tirzepatide and eloralintide.
A potential “winning approach”
The results were presented at the European Association for the Study of Diabetes in Milan, Italy. On Wednesday, Lilly announced plans to advance the combination product to Phase 3 studies by the end of 2026.
Ahead of the Phase 2 data, some analysts said the study positioned Lilly’s combination regimen as a direct comparison to Novo’s next-generation obesity treatment, CagriSema, which combines drugs targeting amylin and GLP-1.
Custer said the combined diet could “prove to be a really winning approach.”
“This very physiological approach of combining GLP-1, GIP and amylin, which are three nutrient-stimulated hormones that your body naturally releases in response to food and which promote satiety, could well be a widely used medicine,” he said. “You’re sort of lightly engaging three hormonal systems rather than blowing up one of them.”
Ahead of Lilly’s data, Leerink Partners analyst David Risinger said he sees “mega-blockbuster” sales for Lilly’s amylin-targeting drug, eloralintide, which is also being studied as a standalone treatment. He told CNBC that the drug likely had “far greater market potential than the Street currently believes,” noting that there are “millions” of patients who have not seen results from existing GLP-1 treatments or who could not tolerate their side effects.
Risinger added that Lilly’s combination therapy may also serve as an alternative to the company’s other next-generation obesity drug that also targets three other gut hormones. This treatment, retatrutide, targets GLP-1, GIP, and another hormone called glucagon, and has shown some of the highest levels of weight loss seen in clinical trials to date.
Wednesday’s results reinforce positive results seen in a Phase 1 trial of the amylin-tirzepatide combination regimen.
In the study, adding a 3-milligram dose of eloralintide to a 5-milligram dose of tirzepatide resulted in 17% weight loss over 16 weeks in obese adults. This compares to a 10% weight loss with the same dose of tirzepatide alone, according to Lilly.
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