Lilly Amylin-Tirzepatide Combo Shows Strong Weight Loss in Trial

Eli Lilly said on September 30 that its experimental obesity treatment EloraTZP, which combines the amylin-targeting drug eloralintide with the approved drug tirzepatide, produced significant weight loss and improved blood-sugar control in a mid-stage trial of adults with obesity and type 2 diabetes. Lilly unveiled the findings during the European Association for the Study of Diabetes's yearly gathering, held in Milan.¹³⁴

Trial results

According to Lilly, the mid-stage study drew 367 participants from the US and Argentina who had type 2 diabetes and were either obese or overweight. Participants were randomly assigned to receive tirzepatide alone, tirzepatide combined with eloralintide at various doses, or placebo.³²

After 48 weeks, according to Lilly's own release, participants on the highest-dose EloraTZP combination lost an average of 54.1 pounds, or 23.3 percent of body weight, compared with 34.4 pounds, or 14.8 percent, for those on 15-milligram tirzepatide alone, and 7.0 pounds, or 3.0 percent, for the placebo group. New Scientist reported the same high-dose group loss in metric terms as 24.5 kilograms.³²⁴

Lilly also reported that eloralintide used on its own, without tirzepatide, reduced body weight by up to 28.6 pounds, or 12.3 percent.³⁵

Blood sugar control

The combination also affected blood-sugar levels more than tirzepatide alone, according to Lilly. The company reported that EloraTZP lowered A1C, a measure of average blood sugar, by up to 2.9 percent, compared with up to 2.4 percent for tirzepatide alone and roughly 0.3 percent for placebo.¹²⁵

Liana K. Billings, associated with the trial, said, "Obesity and type 2 diabetes are interconnected, and we are seeing the potential benefit of targeting multiple hormonal pathways to address both." She added, "Across the dose combinations studied with eloralintide and tirzepatide, participants had substantial weight loss alongside meaningful reductions in A1C."³

Side effects and tolerability

Lilly and other outlets reported that the most common side effects across the trial were gastrointestinal, including diarrhoea, nausea and vomiting, and were generally described as mild or moderate.¹²³

Discontinuation rates due to side effects were higher in the combination arms, ranging from 10.8 percent to 27.0 percent, compared with roughly 2.9 to 3 percent for tirzepatide alone and about 16.7 to 17 percent for placebo, according to Lilly and Reuters. STAT noted that the high dropout rates in some combo arms may raise questions about tolerability.¹³⁴⁵

Ken Custer, president of Lilly Cardiometabolic Health, addressed the discontinuation data at a press conference, saying, "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," adding that this makes it "very hard to actually profile final tolerability of an agent."⁵

Scientific and competitive context

Tirzepatide, the active ingredient in Lilly's approved drug Zepbound, replicates the effects of two hormones that curb appetite, GLP-1 and GIP, and New Scientist has called it the strongest weight-loss medication currently on the market. Eloralintide instead targets amylin, a separate appetite-regulating hormone produced in the pancreas, bringing what New Scientist described as a third hormonal pathway into play alongside tirzepatide's two.²

Dan Skovronsky, Lilly's chief scientific and product officer, said he was "really excited about eloralintide because it is, I think, the first to be preferential and specific for amylin rather than calcitonin," adding, "It's been hard to make specific amylin agonists."⁵

The data were presented during the EASD meeting in Milan, where Novo Nordisk also presented competing obesity and diabetes results the same week, according to Fierce Pharma. Endpoints News reported that EloraTZP's results surpass prior benchmarks including Novo's CagriSema and Lilly's own retatrutide, calling the drug "the latest big name in obesity." BioSpace noted that CagriSema had earlier lost to Zepbound in the REDEFINE 4 trial but outperformed Zepbound in the REIMAGINE 5 trial among adults with type 2 diabetes.⁸⁷⁵

Lilly said it plans to advance an EloraTZP co-formulation into Phase 3 trials by the end of 2026, and Kenneth Custer said, "We are highly encouraged by our Phase 2 results with EloraTZP and look forward to quickly initiating Phase 3 studies."³⁵