EloraTZP Delivers Up to 23.3% Weight Loss in Adults With Obesity and T2D

An investigational combination of eloralintide and tirzepatide (Zepbound, Mounjaro; Eli Lilly and Company), known as EloraTZP, produced mean weight loss of up to 23.3% and mean HbA1c reductions of up to 2.9% over 48 weeks in adults with obesity or overweight and type 2 diabetes (T2D), according to phase 2b data presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan, Italy.^1,2

The findings, in a population in which substantial weight loss has been difficult to achieve, suggest a role for layering amylin-based agents onto incretin therapy.^1,2

Pairing Amylin With Dual Incretin Activity

EloraTZP combines eloralintide, an investigational once-weekly selective amylin receptor agonist previously known as LY3841136, with tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. According to Eli Lilly, the combination was designed to activate all 3 pathways with minimal activity at the calcitonin receptor.^1,2

Eloralintide has shown promise on its own. In a 48-week phase 2 trial of 263 adults with obesity or overweight without T2D, eloralintide monotherapy produced mean weight reductions of up to 20%. That trial followed a phase 1 proof-of-concept study in which gastrointestinal adverse events were infrequent.^3,4

Trial Design and Efficacy

The double-blind, placebo-controlled phase 2b trial (NCT06603571) randomly assigned 367 adults in the United States and Argentina to placebo, eloralintide alone, tirzepatide alone, or 1 of 4 EloraTZP dose combinations, given as separate injections. Participants had a mean baseline body weight of 105.4 kg and a mean baseline HbA1c of 8.1%. The primary end point was percent change in body weight with EloraTZP versus placebo at 48 weeks; all other comparisons were secondary.^1,2

Using the efficacy estimand, mean weight loss was 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 HbA1c reductions were 2.2%, 2.7%, 2.6%, and 2.9%, respectively. Tirzepatide 15 mg alone yielded weight loss of 14.8% and an HbA1c reduction of 2.4%; eloralintide alone produced weight loss of 8.2% to 12.3%, and placebo produced 3.0% and 0.3%, respectively.²

Tolerability and Titration

The most common adverse events were gastrointestinal, generally mild or moderate, and occurred primarily during dose escalation, more often in the combination arms than with either agent alone. Discontinuation due to adverse events ranged from 10.8% to 27.0% across EloraTZP arms, compared with 0% to 10.8% with eloralintide, 2.9% with tirzepatide, and 16.7% with placebo.²

Those events were more frequent when both agents were initiated and escalated at the same time, according to lead author Liana K. Billings, MD, MMSc, vice chair of research in the Department of Medicine at Endeavor Health and clinical associate professor in medicine at the University of Chicago Pritzker School of Medicine.

"If I were using this approach with my patients, I would set expectations from the outset that gastrointestinal symptoms may occur and discuss dietary and lifestyle strategies, as well as short-term medications for symptom relief when needed," Billings told Pharmacy Times. "Importantly, if tolerability is a concern, these data also support a sequential approach. When participants first escalated tirzepatide to 15 mg and then added eloralintide, gastrointestinal adverse event rates were similar to tirzepatide alone, while still achieving excellent weight and glucose-lowering efficacy."

Implications for Treatment Sequencing

"Amylin agonists give us another option for treating obesity and T2D and an opportunity to further individualize therapy," Billings said. "In this trial, adding eloralintide after participants had escalated tirzepatide to 15 mg led to a further increase in the trajectory of weight loss, suggesting that eloralintide could be added when additional weight or HbA1c reduction is needed."

Although the reverse sequence was not studied, Billings said the efficacy and tolerability of eloralintide alone raise the possibility of starting with eloralintide and adding tirzepatide later if additional efficacy is needed. When pharmacists review regimens for patients with T2D, they should note that tirzepatide labeling says hypoglycemia risk may be higher with concomitant insulin or a sulfonylurea. That matters as additional glucose-lowering mechanisms are layered on.²

REFERENCES

1. New investigational drug combining eloralintide and tirzepatide (EloraTZP) led to weight loss of up to 23.3% in people living with obesity and type 2 diabetes. News release. EurekAlert!; European Association for the Study of Diabetes. September 30, 2026. Accessed September 30, 2026. https://www.eurekalert.org/news-releases/1146045

2. 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. News release. Eli Lilly and Company. September 30, 2026. Accessed September 30, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide

3. Bhattachar S, Tham LS, Tidemann-Miller B, Ibriga H, Qu H, Briere DA, Haupt A, Mather KJ, Pratt E. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept. Diabetes Obes Metab. 2026;28(4):2651-2660. doi:10.1111/dom.70439

4. Billings LK, Hsia S, Bays H, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2025;406(10520):2631-2643. doi:10.1016/S0140-6736(25)02155-5