Phase 2b findings presented at the 2026 EASD Annual Meeting showed that EloraTZP — a combination of the selective amylin receptor agonist eloralintide with tirzepatide — delivered body weight reductions of up to 23.3% and A1C decreases of up to 2.9% over 48 weeks in adults carrying excess weight or living with obesity alongside type 2 diabetes, outcomes that surpassed those observed with tirzepatide 15 mg administered alone. The formulation targets three nutrient-stimulated hormonal pathways simultaneously — glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and amylin — while producing limited engagement at the calcitonin receptor. Following a meal, distinct receptors bind to their corresponding hormones, working together to manage appetite and maintain stable blood sugar levels. In a prior phase 2 trial involving adults without type 2 diabetes, eloralintide outperformed placebo in reducing body weight as a standalone therapy; lead author Liana K. Billings, MD, director of clinical and genetics research in diabetes and cardiometabolic disease at Endeavor Health in Evanston, Illinois, noted that obesity and type 2 diabetes are closely linked, and that addressing multiple hormonal pathways simultaneously may offer therapeutic advantages for both conditions. A 48-week, double-blind, placebo-controlled phase 2b study (NCT06603571) enrolled 367 adults living with obesity or overweight alongside type 2 diabetes across trial sites in the US and Argentina, assigning participants to one of four arms: placebo, eloralintide, tirzepatide, or EloraTZP. At the start of the trial, the average body weight among enrolled individuals stood at 105.4 kg, with an average A1C reading of 8.1%. The trial's main outcome measure was the proportional shift in body weight for participants receiving EloraTZP compared with those on placebo, while all remaining comparisons were classified as secondary. Every dosage combination of EloraTZP achieved the trial's principal and secondary outcome measures. At 48 weeks, average body weight declined by 13.2% with the 3 mg eloralintide and 5 mg tirzepatide combination, by 19.4% with 6 mg eloralintide and 5 mg tirzepatide, by 19.9% with 6 mg eloralintide and 10 mg tirzepatide, and by 23.3% with 9 mg eloralintide and 15 mg tirzepatide, according to the efficacy estimand. A1C levels dropped by between 2.2% and 2.9% across the measured outcomes. In contrast, the 15 mg tirzepatide monotherapy arm achieved a 14.8% reduction in body weight alongside a 2.4% drop in A1C levels. Trial participants on eloralintide alone achieved body weight reductions of 8.2% to 12.3% and A1C decreases of 1.1% to 1.4%, compared with those on placebo, who recorded a 3.0% drop in body weight and a 0.3% decline in A1C. Gastrointestinal reactions were the most frequently reported side effects, typically ranging from mild to moderate in severity, with the majority arising during the period of dose escalation. The adverse events were reported at higher rates in the combination treatment groups compared with either eloralintide or tirzepatide administered as monotherapy. Among those receiving EloraTZP, treatment withdrawal owing to unwanted side effects occurred in 10.8% to 27.0% of participants, versus a range of 0% to 10.8% for eloralintide, 2.9% for tirzepatide, and 16.7% for those on placebo. Both compounds were delivered via separate weekly injections throughout the course of the study. Participants in the combination treatment groups started on eloralintide 1 mg or 3 mg alongside tirzepatide 2.5 mg, with doses increasing every four weeks to reach the intended targets; Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, described EloraTZP as the company's next area of development, combining a selective amylin receptor agonist with tirzepatide in what he characterised as a potentially additive and more physiologically aligned approach to metabolic health management. The company intends to launch phase 3 trials of an EloraTZP co-formulation before the close of 2026, employing a refined dose-escalation protocol. The compound is additionally undergoing phase 3 trials as a standalone treatment for obesity. This drug pairing enters a therapeutic area where Novo Nordisk's amylin-based dual therapy, cagrilintide combined with semaglutide (CagriSema), demonstrated greater efficacy than semaglutide as a standalone treatment across phase 3 REIMAGINE trial data.
