Eli Lilly Weight-Loss Trial Tops Zepbound

Eli Lilly weight-loss trial results on Sept. 30, 2026 showed the experimental EloraTZP combination delivered substantially greater weight loss at 48 weeks than tirzepatide, strengthening Lilly’s obesity pipeline while highlighting tolerability and dose-escalation challenges ahead of planned Phase 3 studies.

EloraTZP Phase 2b Results and Retatrutide Phase 3 Findings

Lilly reported Phase 2b results for EloraTZP, a combination of the investigational selective amylin-receptor agonist eloralintide and tirzepatide, the active ingredient in Zepbound. The trial enrolled 367 adults with obesity or overweight and Type 2 diabetes. At the highest tested dose, EloraTZP produced an average 23.3% reduction in body weight at 48 weeks, compared with 14.8% for the highest tirzepatide dose and 3.0% for placebo.

The combination also improved glucose control, reducing hemoglobin A1C—a measure of average blood glucose over two to three months—by 2.9 percentage points versus 2.4 points with 15 mg tirzepatide and 0.3 points with placebo. Treatment discontinuations due to adverse events ranged from 10.8% to 27.0% across EloraTZP doses, higher than the 2.9% rate with tirzepatide alone. Eloralintide monotherapy discontinuations ranged from 0% to 10.8%, while placebo discontinuations were 16.7%. The most common adverse events were mild to moderate gastrointestinal issues occurring mainly during dose escalation. Lilly attributed the higher discontinuation rates partly to simultaneous escalation of two therapies and plans to refine dose-escalation schedules in future trials.

Separately, Lilly disclosed Phase 3 results for retatrutide, an investigational triple agonist targeting GIP, GLP-1, and glucagon receptors. The TRIUMPH-2 trial randomized 1,152 adults with Type 2 diabetes and overweight or obesity equally to retatrutide doses of 4 mg, 9 mg, 12 mg, or placebo over 80 weeks. Reports described average weight reductions of up to 20.8%, or roughly 49.6 pounds, at 80 weeks. Discontinuation rates due to adverse events varied by dose: 3.8% at 4 mg, 11.6% at 9 mg, and 7.7% at 12 mg, compared with 4.9% for placebo. Retatrutide remains investigational and is not approved.

The EloraTZP and retatrutide data are not directly comparable due to differences in molecules, study designs, patient populations, doses, and time points. EloraTZP’s top result came from a within-trial comparison against tirzepatide at 48 weeks, while retatrutide’s figure was observed in a separate placebo-controlled study at 80 weeks.

Lilly plans to begin Phase 3 studies of EloraTZP by the end of 2026. A secondary report indicated Lilly intends to submit an FDA approval application for retatrutide in early 2027, though this timeline was not independently confirmed in the company’s Sept. 29 press release.