EloraTZP, an investigational combination of the selective amylin receptor agonist eloralintide and tirzepatide, reduced body weight by up to 23.3% and A1C by up to 2.9% at 48 weeks in adults with obesity or overweight and type 2 diabetes, exceeding results with tirzepatide 15 mg alone, according to phase 2b data presented at the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting.1
The combination is designed to activate 3 nutrient-stimulated hormone pathways at once: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and amylin, with minimal activity at the calcitonin receptor.1
Each hormone acts through its own receptor after a meal to help regulate hunger and blood glucose.2 Eloralintide previously demonstrated superiority to placebo for weight reduction as monotherapy in a phase 2 trial of adults without type 2 diabetes.3
"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, MD, director of clinical and genetics research in diabetes and cardiometabolic disease at Endeavor Health in Evanston, Illinois, and lead author.
EloraTZP Phase 2b Weight Loss and A1C Results
The 48-week, double-blind, placebo-controlled phase 2b trial (NCT06603571) randomized 367 adults with obesity or overweight and type 2 diabetes in the US and Argentina to placebo, eloralintide, tirzepatide, or EloraTZP.1 Participants had a mean baseline body weight of 105.4 kg and a mean baseline A1C of 8.1%. The primary endpoint was percent change in body weight with EloraTZP versus placebo, with all other comparisons designated as secondary endpoints.1
All EloraTZP dose combinations met the primary and secondary endpoints.1 Based on the efficacy estimand, mean weight reductions at 48 weeks were 13.2% with eloralintide 3 mg plus tirzepatide 5 mg, 19.4% with eloralintide 6 mg plus tirzepatide 5 mg, 19.9% with eloralintide 6 mg plus tirzepatide 10 mg, and 23.3% with eloralintide 9 mg plus tirzepatide 15 mg. Corresponding A1C reductions ranged from 2.2% to 2.9%.1
By comparison, tirzepatide 15 mg alone reduced body weight by 14.8% and A1C by 2.4%.1 Eloralintide monotherapy lowered body weight by 8.2% to 12.3% and A1C by 1.1% to 1.4%, while participants receiving placebo lost 3.0% of body weight with a 0.3% reduction in A1C.1
EloraTZP Safety, Tolerability, and Phase 3 Plans
The most common adverse events were gastrointestinal and generally mild or moderate, occurring primarily during dose escalation.1 These events occurred more frequently in the combination arms than with eloralintide or tirzepatide alone. Discontinuation rates due to adverse events ranged from 10.8% to 27.0% with EloraTZP, compared with 0% to 10.8% with eloralintide, 2.9% with tirzepatide, and 16.7% with placebo.1
In the trial, eloralintide and tirzepatide were administered as separate once-weekly injections.1 Participants in the combination arms began at eloralintide 1 mg or 3 mg and tirzepatide 2.5 mg, escalating every 4 weeks until reaching their target doses.1
"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," said Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health.
Lilly plans to initiate phase 3 trials of an EloraTZP co-formulation product by the end of 2026 using an optimized escalation schedule.1 Eloralintide is also in phase 3 development as a single agent for obesity. The combination enters a field where Novo Nordisk's amylin-based combination, cagrilintide and semaglutide (CagriSema), has shown superiority over semaglutide alone in phase 3 REIMAGINE trials.4
References
Eli Lilly and Company. Lilly's EloraTZP (combination of eloralintide and tirzepatide) delivered greater weight loss and A1C reduction vs. tirzepatide 15 mg in adults with obesity and type 2 diabetes. Published September 30, 2026. Accessed September 30, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide
Hayes MR, Mietlicki-Baase EG, Kanoski SE, De Jonghe BC. Incretins and amylin: neuroendocrine communication between the gut, pancreas, and brain in control of food intake and blood glucose. Annu Rev Nutr. 2014;34:237-260. doi:10.1146/annurev-nutr-071812-161201
