An experimental pairing of Eli Lilly's amylin drug eloralintide with tirzepatide, the active ingredient in Mounjaro and Zepbound, produced an average 23.3% weight loss over 48 weeks in adults with obesity and type 2 diabetes, according to Phase 2 results released by Lilly Sept. 30 at the EASD meeting in Milan.
Participants on the highest-dose combination lost about 54 pounds, compared with about 34 pounds, or 14.8%, on the top dose of tirzepatide alone. The combination, called EloraTZP, also lowered A1C more.
The catch is tolerability. Up to 27% of people on the combination stopped treatment because of side effects, compared with 2.9% on tirzepatide alone. The trial was mid-stage and run by Lilly, and the full results have not yet appeared in a peer-reviewed journal.
A Bigger Drop in Weight and Blood Sugar
The 48-week trial randomly assigned 367 adults in the United States and Argentina to placebo, one of three doses of eloralintide alone, tirzepatide 15 mg alone, or one of four combination doses. Participants started at an average of about 232 pounds with an average A1C of 8.1%. Neither participants nor investigators knew who received which treatment.
The highest-dose combination, eloralintide 9 mg plus tirzepatide 15 mg, lowered A1C by 2.9 percentage points, compared with 2.4 on tirzepatide alone and 0.3 on placebo. Lower combination doses produced 13.2% to 19.9% weight loss. Eloralintide on its own produced 8.2% at 3 mg, 12.3% at 6 mg, and 11.1% at 9 mg, while the placebo group lost 3.0%. The trial is registered as NCT06603571.
The gap with tirzepatide alone was large for a diabetes population. In a note to clients reported by Fierce Biotech, Citi analysts called the combination's result "comparable to tirzepatide in patients without T2D," a group that usually loses more weight. MedicalDaily's preview of the EASD 2026 meeting flagged these results as among the most anticipated.
These figures use what Lilly calls the efficacy estimand, which estimates results had all participants stayed on treatment for 48 weeks. Because many people stopped, real-world results could be smaller.
"Obesity and type 2 diabetes are interconnected, and we are seeing the potential benefit of targeting multiple hormonal pathways to address both," said lead author Dr. Liana Billings of Endeavor Health in Evanston, Illinois.
Amylin Drugs and How They Work
Amylin is a hormone released by the pancreas along with insulin after meals. It helps signal fullness and slows how quickly the stomach empties. Eloralintide is a once-weekly shot that selectively activates amylin receptors and, according to Lilly, is designed to reduce calorie intake by increasing feelings of fullness.
Tirzepatide works on two other gut hormones, GLP-1 and GIP. Combining the drugs targets three appetite and blood sugar pathways at once. "EloraTZP represents our next frontier," said Kenneth Custer, executive vice president of Lilly and president of Lilly Cardiometabolic Health.
Eloralintide alone produced up to 20.1% weight loss at 48 weeks in an earlier Phase 2 trial of people without diabetes, published in The Lancet. In this diabetes trial, eloralintide alone produced 8.2% to 12.3% weight loss. People with type 2 diabetes typically lose less weight on these drugs than people without it.
Novo Nordisk is developing a competing amylin combination, CagriSema, which pairs cagrilintide with semaglutide. Fierce Biotech noted that CagriSema missed one of its goals in a Phase 3 study in people with type 2 diabetes in August. For patients, combinations could eventually mean more weight loss from one weekly shot, though likely with more side effects to manage.
Side Effects and the Road to Phase 3
Lilly said the most common side effects were stomach-related, generally mild or moderate, and occurred mainly while doses were being increased. They were more frequent with the combination than with either drug alone. Lilly did not release rates of nausea or vomiting.
Discontinuation due to side effects ranged from 10.8% to 27.0% across the combination groups. In the placebo group, 16.7% stopped because of side effects, an unusually high rate that complicates comparisons.
Citi analysts wrote that the weight loss was "comfortably above our 17% bar," Fierce Biotech reported. They suggested the dropout rate may reflect starting both drugs at once and said an "optimized phase 3 titration could preserve efficacy while improving adherence."
Lilly plans to start Phase 3 trials of a single-injection version of EloraTZP by the end of 2026, using an optimized dose escalation schedule. Approval, if it comes, is likely years away. Phase 3 studies will need to show that the new schedule reduces dropouts while keeping most of the weight loss, and they will be far larger and longer than this 367-person trial.
For now, EloraTZP is not available outside clinical trials. People with type 2 diabetes and obesity have approved options, including tirzepatide and semaglutide. Insurance coverage for those drugs varies, and patients can ask their clinician about eligibility, cost, and side effects. Anyone interested in trials can search ClinicalTrials.gov.
Key Questions Answered
What is EloraTZP? It is Lilly's experimental combination of eloralintide, an amylin-based drug, and tirzepatide, the active ingredient in Mounjaro and Zepbound.
How much weight did people lose? The top dose produced 23.3% average weight loss at 48 weeks, compared with 14.8% with tirzepatide alone, assuming everyone stayed on treatment.
What were the side effects? Mostly nausea and other stomach problems. Up to 27% on the combination stopped because of side effects.
Who funded the study? Eli Lilly sponsored the trial.
Is EloraTZP available? No. It is investigational, and Lilly plans to start Phase 3 trials by the end of 2026.
What is amylin? A hormone released by the pancreas with insulin that promotes fullness and slows stomach emptying.
Published by Medicaldaily.com
