Lilly Obesity Combination Beats Tirzepatide on Weight Loss, but Dropouts Rise

Eli Lilly (NYSE: LLY), maker of the obesity drug Zepbound, has reported that its experimental EloraTZP combination produced up to 23.3% average weight loss at 48 weeks in a mid-stage trial, against 14.8% for tirzepatide alone. The data were presented at the EASD diabetes meeting in Milan.

Lilly shares were up 0.9% at $1,194.93 at 3.18pm London time, from yesterday’s close of $1,184.63. That leaves them 7.6% below the 52-week high of $1,292.65, reached intraday on the 19th of August.

EloraTZP pairs eloralintide, which acts on amylin, a satiety hormone, with tirzepatide, the active ingredient in Zepbound and Mounjaro. The trial enrolled 367 adults with obesity or overweight and type 2 diabetes. Lilly said all dose combinations met the primary and secondary endpoints.

The 23.3% is the efficacy estimand, a measure that ignores stopped treatment. Tirzepatide alone delivered 14.8%, placebo 3% and eloralintide alone up to 12.3%. On blood sugar, the highest-dose combination cut A1C, a measure of average blood sugar over two to three months, by 2.9%, against 2.4% for 15mg Zepbound and 0.3% for placebo.

The catch is tolerability. Discontinuation because of adverse events ran from 10.8% to 27% across combination doses, against 2.9% on tirzepatide alone. Side effects were mainly gastrointestinal, generally mild to moderate, and mostly during dose increases.

Ken Custer, President of Lilly Cardio Metabolic Health, put the dropouts down to trial design:

These are relatively short studies—in this case, 48 weeks—and we were ramping individuals up multiple doses for two different drugs at the same time

Ken Custer, Lilly

The study invites a direct comparison with Novo Nordisk’s CagriSema, a rival amylin-based combination. David Risinger of Leerink expects “mega-blockbuster” sales for eloralintide.

Lilly plans to start Phase 3, the final large-scale stage of testing, in the fourth quarter of 2026. It will be a longer study with an optimised dose-escalation schedule, alongside work on a single-injection co-formulation.