EloraTZP—a combination of an amylin asset and Eli Lilly’s approved obesity drug Zepbound—made a clean sweep of the primary and secondary endpoints in a mid-stage trial of adults with obesity and type 2 diabetes, setting up the launch of a Phase 3 trial before the end of the year.
Eli Lilly introduced a new name into the weight loss lexicon on Wednesday, revealing that EloraTZP—a combination of the amylin agonist eloralintide and Lilly’s powerhouse dual GIP/GLP-1 agonist Zepbound—elicited up to 23.3% average weight loss at 48 weeks in a mid-stage trial, compared to 14.8% for tirzepatide alone and 3% for placebo.
Lilly presented the data from the Phase 2b trial of 367 adults with obesity or overweight and type 2 diabetes at the European Association for the Study of Diabetes (EASD) annual meeting in Milan, Italy on Wednesday. The results were based on efficacy estimand, ignoring discontinuations or other deviations from the assigned regimen of the study drug.
In addition to hitting the study’s primary endpoint of superior weight loss versus placebo, EloraTZP improved blood sugar control. Participants taking the highest dose of the combo saw A1C—a measure of average blood glucose over the past 2–3 months—lowered by an average of 2.9%, compared to 2.4% for those on 15 mg Zepbound and 0.3% for placebo.
All dose combinations of eloralintide with Zepbound met the study’s primary and secondary endpoints, Lilly said, “delivering substantial weight loss and A1C reduction.”
Based on the results, Lilly plans to launch Phase 3 trials of the combo in the fourth quarter.
While EloraTZP’s weight loss and A1C benefits were clear, the combination’s safety profile was more muddled. Across the dose ranges, participants on EloraTZP discontinued treatment due to adverse events at a rate of between 10.8% and 27%. This was compared to 0% to 10.8% for eloralintide alone, 2.9% for tirzepatide only and 16.7% for placebo.
During a press conference at EASD on Monday, Ken Custer, president of Lilly Cardio Metabolic Health, said that the study design made it “very hard to actually profile final tolerability of an agent.”
“These are relatively short studies—in this case, 48 weeks—and we were ramping individuals up multiple doses for two different drugs at the same time,” Custer said in response to a question about the discontinuation rates. The Phase 3 study will be longer and employ an optimized escalation schedule, he added.
All about amylin
Eloralintide also performed well as a monotherapy, reducing body weight by up to an average of 12.3%. But the new study clearly points to higher efficacy for the combination of the amylin asset with Lilly’s established weight loss drug.
Indeed, EloraTZP’s 23.3% weight loss in the new trial also beat eloralintide’s performance in a Phase 2 study that read out in November 2025, during which 9 mg of the amylin agonist generated 20.1% weight loss after 48 weeks. These results exceeded analyst expectations and highlighted a “potentially best in class profile,” BMO Capital Markets said at the time. The drug is also being tested as monotherapy in the Phase 3 ENLIGHTEN-1 trial in adults with obesity or overweight who do not have type 2 diabetes. Primary completion is set for March 2028.
Lilly is “really excited about eloralintide because it is, I think, the first to be preferential and specific for amylin rather than calcitonin,” Chief Scientific and Product Officer Dan Skovronsky said on the media call. “It’s been hard to make specific amylin agonists,” he explained, because in addition to targeting amylin receptors in the pancreas, the molecules will often work on the calcitonin system in the thyroid, affecting calcium metabolism.
Meanwhile, Lilly’s chief rival Novo shared a different perspective during a physician event on Monday.
“Presenters highlighted the possibility that calcitonin-receptor engagement could help protect bone density, while also discussing amylin’s role in improving leptin responsiveness,” BMO Capital Markets said in a note to investors the same day. Leptin is a hormone produced mainly by fat cells that helps signal satiety to the brain.
Novo has CagriSema in the amylin combo class, with the asset pairing semaglutide with the long-acting amylin analog cagrilintide. In February, CagriSema fell to Zepbound in the head-to-head REDEFINE 4 study, generating 23% weight loss at 84 weeks vs. the latter’s 25.5% in people with obesity. However, in the REIMAGINE 5 trial reported last week, the combo drug bested Zepbound at week 60 in adults with type 2 diabetes, eliciting 12.4% weight loss compared to Zepbound’s 9.1%.
