Lilly’s EloraTZP combination of eloralintide and tirzepatide delivered up to 23.3% weight loss and 2.9% A1C reduction in a Phase 2b trial.
Written By: Khushi Patel, PharmD
Reviewed by: Pharmacally Editorial Team
Eli Lilly reported 48-week Phase 2b results for EloraTZP, an investigational combination of eloralintide, a selective amylin receptor agonist, and tirzepatide, a dual GIP and GLP-1 receptor agonist. Across the combination regimens, EloraTZP met the study’s primary and secondary endpoints and produced greater reductions in body weight and A1C than either agent alone.
The highest-dose combination, eloralintide 9 mg plus tirzepatide 15 mg, produced an average 23.3% reduction in body weight, equivalent to 54.1 lb (24.5 kg), and reduced A1C by 2.9 percentage points at 48 weeks. Tirzepatide 15 mg alone produced 14.8% weight loss, or 34.4 lb, and a 2.4-point A1C reduction.
The study’s primary endpoint tested EloraTZP against placebo for percentage change in body weight. Comparisons between EloraTZP and tirzepatide were secondary endpoints.
Combining Amylin and Incretin Pathways
EloraTZP combines two complementary hormonal approaches to metabolic regulation. Eloralintide activates the amylin receptor, while tirzepatide activates GIP and GLP-1 receptors. These nutrient-responsive pathways influence appetite, satiety and glucose regulation through distinct mechanisms.
Eloralintide alone produced up to 12.3% average weight loss and a 1.4-point A1C reduction. The results suggest that adding the amylin agonist to tirzepatide can extend the weight and glycemic effects achieved with incretin-based treatment alone.
48-Week Phase 2b Study
The randomized, double-blind, placebo-controlled Phase 2b study (NCT06603571) enrolled 367 adults in the U.S. and Argentina with obesity or overweight and type 2 diabetes. Participants were assigned across placebo, eloralintide, tirzepatide, and combination-treatment groups.
Combination regimens included eloralintide doses of 3 or 6 mg with tirzepatide 5 mg, as well as 6 mg plus tirzepatide 10 mg and 9 mg plus tirzepatide 15 mg. Treatment used stepwise dose escalation, with increases generally occurring every four weeks.
Gastrointestinal adverse events were the most common safety findings and were generally mild to moderate, occurring mainly during dose escalation. These events occurred more frequently with combination treatment than with either agent alone. Treatment discontinuation because of adverse events ranged from 10.8% to 27.0% across EloraTZP groups, compared with 2.9% for tirzepatide and 16.7% for placebo.
Phase 3 Development Planned for Late 2026
Lilly plans to initiate Phase 3 studies of an EloraTZP co-formulation by the end of 2026, using an optimized dose-escalation schedule. Eloralintide is also being evaluated separately in Phase 3 obesity studies.
The Phase 2b findings provide clinical support for combining amylin and incretin signaling, but larger Phase 3 trials will need to establish the durability, safety and clinical benefit of the combination in broader populations. EloraTZP remains investigational and has not received regulatory approval for obesity or type 2 diabetes.
Reference
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, Eli Lilly, 30 September 2026
A Study to Investigate Weight Management with LY3841136 and Tirzepatide (LY3298176), Alone or in Combination, in Adult Participants with Obesity or Overweight with Type 2 Diabetes, ClinicalTrials.gov ID NCT06603571
About the Writer
Khushi Patel is a Pharm.D (Linkedin) professional with a strong foundation in clinical pharmacy, patient-centered care, regulatory affairs, and pharmacovigilance, with published work on Brugada syndrome.
Her interests include regulatory affairs, pharmacovigilance, guideline integration, multimodal therapy, pharmacogenomics, and antibiogram utilization, with a focus on evidence-based clinical decision-making and medication safety.
As a Pharmacally healthcare writer, she translates clinical and scientific evidence into clear, accurate, and clinically relevant healthcare content, while continuously developing her expertise in evolving pharmacy practice.