Lilly's EloraTZP cut body weight by up to 23.3% in Phase 2b trial

Results at 48 weeks

The 48-week Phase 2b trial enrolled 367 adults with obesity or overweight and type 2 diabetes, Lilly said. The company presented the data at the 62nd annual meeting of the European Association for the Study of Diabetes in Milan. Lilly said all combinations of EloraTZP met the trial's primary and secondary endpoints. Liana Billings, the lead author, said obesity and type 2 diabetes are interconnected and that targeting multiple hormonal pathways could address both.

The highest dose, 9 mg of eloralintide with 15 mg of tirzepatide, produced 23.3% weight loss, or 54.1 lbs, at 48 weeks. Tirzepatide 15 mg alone produced 14.8%, or 34.4 lbs. The combination lowered A1C by 2.9 percentage points, against 2.4 for tirzepatide 15 mg and 0.3 for placebo. Participants began at an average 232.4 lbs and an A1C of 8.1%.

Eloralintide alone reduced body weight by up to 12.3%, or 28.6 lbs, and A1C by 1.4 percentage points. Placebo produced 3% weight loss. The efficacy figures use an estimand that ignores discontinuations and other deviations from the assigned regimen, Lilly said.

Tolerability

Gastrointestinal side effects were the most common. They were generally mild or moderate and occurred mainly during dose escalation, Lilly said. They appeared more often in the combination arms than with either single drug. Discontinuation due to adverse events ran from 10.8% to 27.0% on EloraTZP, against 2.9% on tirzepatide, 0% to 10.8% on eloralintide and 16.7% on placebo.

Kenneth Custer, president of Lilly Cardiometabolic Health, told a press conference at EASD in Milan that the design made it "very hard to actually profile final tolerability of an agent." He said Phase 3 will run longer and use an optimized escalation schedule. BNP Paribas wrote in an Oct. 5 note that the results were "met with mixed reaction owing to the tolerability trade-off," BioSpace reported.

What the combination does

EloraTZP combines eloralintide, a selective amylin receptor agonist, with tirzepatide, a dual GIP and GLP-1 receptor agonist sold as Zepbound and Mounjaro. Lilly said the combination was designed to activate GIP, GLP-1 and amylin with minimal activity at the calcitonin receptor. In the Phase 2b study, the two drugs were given as separate injections.

Lilly's shares rose as much as 2.6% before settling 0.5% higher, while Novo Nordisk slipped 0.3%, Investing.com reported.

Phase 3

Lilly plans to start Phase 3 trials of EloraTZP in the fourth quarter of 2026. It will advance a co-formulation product, with both drugs in a single product rather than two injections, by the end of 2026 using an optimized escalation schedule. Eloralintide is also in Phase 3 alone in the ENLIGHTEN-1 trial in adults with obesity or overweight who do not have type 2 diabetes, with primary completion set for March 2028.