Eli Lilly on Wednesday said its experimental combination regimen showed greater weight loss than a high dose of its top-selling drug, tirzepatide, alone in a mid-stage trial on patients with obesity and Type 2 diabetes.
The combo therapy met the study’s main goals in a population that typically struggles to lose weight. The results boost hopes that it could serve as an alternative blockbuster treatment option for people who didn’t respond to or see the results they wanted on the current GLP-1 products on the market. Lilly said it plans to start Phase 3 trials on the regimen at the end of the year.
The combination treatment combines Lilly’s experimental drug eloralintide, which targets amylin – a hormone in the pancreas 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 hitting all three pathways, including amylin, can further reduce appetite and improve weight loss – and the combo drug did just that in the 48-week Phase 2 trial.
People taking the highest dose of the combo regimen lost up to 23.3% of their weight, or around 54 pounds, on average. That treatment combined 9 milligrams of the amylin drug and 15 milligrams of tirzepatide.
Meanwhile, patients taking only a 15-milligram dose of tirzepatide saw 14.8% weight loss, or 34.4 pounds, on average. Those who took eloralintide alone lost up to 12.3% of their weight, or 28.6 pounds, on average.
“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 a eloralintide on its own. The ability to combine them together and provide even greater weight loss – that’s definitely one obvious” benefit of the new regimen.
Lilly signage during a groundbreaking ceremony for Eli Lilly and Company’s pharmaceutical manufacturing campus at Generation Park in Houston, Texas, US, on Monday, Sept. 21, 2026.
Mark Felix | Bloomberg | Getty Images
The combo treatment also lowered a key measure of blood sugar levels – A1C – by up to 2.9% on average. Higher-dose tirzepatide reduced A1C by up to 2.4% on average, while the amylin drug lowered it by up to 1.4% on average.
Lilly may face more questions from investors and the medical community about how well patients tolerate and stay on the highly effective combination therapy.
More patients on the combo regimen – 10.8% to 27%, depending on the dose – discontinued treatment due to side effects compared to the 2.9% of people on tirzepatide alone in the trial.
Up to 10.8% of people on the amylin drug alone discontinued treatment due to side effects, compared to 16.7% with placebo.
Lilly said the side effects were more frequent in groups taking the combination regimen compared to tirzepatide or the amylin drug alone. The most common side effects of the combo therapy were gastrointestinal-related, generally mild or moderate in severity, and mainly occurred when patients increased doses in the trial.
But Custer cautioned against reading too much into the combo regimen’s discontinuation rates in Phase 2. He noted that the highest dose of tirzepatide similarly showed elevated rates, around 25%, in a mid-stage trial back in 2018.
“It’s probably not the best indicator of the tolerability of a medicine,” Custer told CNBC. “We do things in Phase 1 and Phase 2 to test what the molecule can do from an efficacy perspective. We also learn from those studies about how we should administer them, and then we make changes. We do this every time.”
Lilly plans to adjust the dosing regimens for the combo treatment in Phase 3 trials, “and we expect that we’ll end up with a very favorable balance of efficacy and tolerability,” Custer added.
Lilly is also planning to advance a co-formulation of the two drugs in Phase 3 trials, meaning that patients will only need to administer one injection with both tirzepatide and eloralintide.
A potential ‘winning approach’
Results were presented at the European Association for the Study of Diabetes in Milan, Italy. On Wednesday, Lilly said it plans to advance the combo product into Phase 3 studies by the end of 2026.
Ahead of the Phase 2 data, some analysts said the study positions 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 combination regimen could “turn out 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 releases naturally in response to food and promotes satiety, putting those things together may just make for a drug that is broadly used,” he said. “You’re sort of lightly engaging three hormone systems rather than blasting any 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 the drug likely has “much greater market potential than the Street currently realized,” noting that there are “millions” of patients who didn’t see results from existing GLP-1 treatments or couldn’t tolerate their side effects.
Risinger added that Lilly’s combination therapy can also serve as an alternative to the company’s other next-generation obesity drug that also targets three other gut hormones. That treatment, retatrutide, targets GLP-1, GIP and another hormone called glucagon, and has shown some of the highest levels of weight loss seen to date in clinical trials.
Wednesday’s results reinforce the positive results seen in a Phase 1 trial on the combo amylin-tirzepatide regimen.
In the study, adding a 3-milligram dose of eloralintide to a 5-milligram dose of tirzepatide led to 17% weight loss over 16 weeks in adults with obesity. That compares to 10% weight loss with that same dose of tirzepatide alone, according to Lilly.
