EloraTZP Phase 2b Trial Beats Tirzepatide on Weight and A1C

The EloraTZP phase 2b trial tested eloralintide, a selective amylin receptor agonist, together with tirzepatide, the dual GIP and GLP-1 receptor agonist sold as Zepbound and Mounjaro. The combination produced greater weight loss and blood sugar reductions than either agent alone in adults with obesity or overweight and type 2 diabetes. At 48 weeks, the highest dose combination lowered body weight by an average of 54.1 lbs (23.3%) and A1C by 2.9%, compared with 34.4 lbs (14.8%) and 2.4% for tirzepatide 15 mg.

Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), reported the results on 30 September 2026 and presented them at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy. The study randomized 367 participants in the United States and Argentina, and all combinations met the primary and secondary endpoints.

Lilly developed EloraTZP to activate three nutrient-stimulated hormones at once: GIP, GLP-1 and amylin, with minimal activity at the calcitonin receptor. The body releases these substances after eating, and each acts through its own receptor to help regulate hunger and blood sugar.

Ad

How EloraTZP combines three hormone pathways

Tirzepatide, the active ingredient in Zepbound and Mounjaro, is the first approved dual GIP and GLP-1 receptor agonist. Eloralintide is a once-weekly selective amylin receptor agonist previously known as LY3841136, and Lilly describes its likely effect as reducing calorie intake by acting on satiety, the feeling of fullness. Pairing the two engages the amylin and incretin pathways at the same time.

“Obesity and type 2 diabetes are interconnected, and we are seeing the potential benefit of targeting multiple hormonal pathways to address both,” said Liana K. Billings, M.D., Director of Clinical and Genetics Research in Diabetes and Cardiometabolic Disease at Endeavor Health, Evanston, Illinois, and lead author of the study. “Across the dose combinations studied with eloralintide and tirzepatide, participants had substantial weight loss alongside meaningful reductions in A1C. These are outcomes that matter to patients. We need to continue building on these findings so that, in the future, we can offer patients more treatment options that address both weight and glucose and better reflect the complexity of living with type 2 diabetes and obesity.”

What the EloraTZP phase 2b trial measured

The study (NCT06603571) was a 48-week, parallel-group, double-blind, placebo-controlled trial of eloralintide and Zepbound given alone or in combination. Its primary objective was to show that eloralintide combined with Zepbound is superior to placebo in percent change in body weight from baseline at 48 weeks. All other comparisons were secondary endpoints. Participants entered with an average baseline weight of 232.4 lbs (105.4 kg) and an average A1C of 8.1%.

Reporting uses the efficacy estimand, which represents efficacy had all randomized participants remained on study intervention for the full 48 weeks, with possible dose interruptions or modifications.

Weight and A1C results across the dose combinations

Source: Eli Lilly and Company, Phase 2 efficacy estimand results. The primary endpoint was percent change in body weight for EloraTZP vs. placebo; all other comparisons were secondary endpoints.

Eloralintide alone reduced body weight by up to an average of 28.6 lbs (12.3%) and A1C by up to 1.4%. Tirzepatide 15 mg reduced body weight by 34.4 lbs (14.8%) and A1C by 2.4%. The combination at 9 mg plus 15 mg exceeded both, producing an 8.5 percentage point weight-loss advantage and a 0.5 percentage point A1C advantage over tirzepatide 15 mg.

Phase 3 plans and Lilly’s metabolic pipeline

Lilly plans to start Phase 3 studies of an EloraTZP co-formulation product by the end of 2026 using an optimized escalation schedule. The Phase 2b trial used separate injections. Eloralintide is also in Phase 3 as a single agent for obesity, and a separate Phase 2b study (NCT06230523) compared once-weekly eloralintide with placebo in adults with obesity or overweight and at least one weight-related comorbidity but without type 2 diabetes.

“Lilly continues to pioneer new medicines for people living with obesity and diabetes, building on our scientific track record with tirzepatide, the first approved GIP and GLP-1 dual agonist, and retatrutide, our investigational triple agonist,” said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. “EloraTZP represents our next frontier, pairing a selective amylin receptor agonist with tirzepatide, which could be an additive and more physiological approach to managing metabolic health. We are highly encouraged by our Phase 2 results with EloraTZP and look forward to quickly initiating Phase 3 studies.”

What the results mean for payers and health economics

For cost-effectiveness modelling, the incremental 8.5 percentage point weight-loss difference and 0.5 percentage point A1C difference against tirzepatide 15 mg are the inputs that matter, weighed against a combination price that has not been announced. The discontinuation spread, which reaches 27.0% in the highest-dose combination arm against 2.9% for tirzepatide 15 mg, bears directly on real-world persistence, on the drug costs of abandoned treatment and on the sequencing rules payers are already writing for incretin therapies.

Lilly frames the optimized escalation schedule for the co-formulation as its answer to that tolerability gap, but the Phase 3 program will have to show it holds the efficacy differential. Until then, the combination is investigational. Zepbound is indicated in the United States for adults with obesity or some adults who are overweight with at least one weight-related medical condition, and is also FDA-approved for adults with moderate-to-severe obstructive sleep apnea and obesity, used with a reduced-calorie diet and increased physical activity.

Source: Eli Lilly and Company news release, 30 September 2026.