Lilly's Zepbound-plus-amylin combo hits 23.3% weight loss, but up to 27% quit on side effects

Eli Lilly said its experimental combination of eloralintide, an amylin drug, and tirzepatide, the active ingredient in Zepbound and Mounjaro, produced average weight loss of 23.3% at 48 weeks at the highest dose in a Phase 2b trial, against 14.8% for tirzepatide 15 mg alone and 3.0% for placebo, according to the company's press release. The results, for a regimen Lilly calls EloraTZP, were presented at the European Association for the Study of Diabetes meeting in Milan.

The trial enrolled 367 adults with obesity or overweight and type 2 diabetes in the U.S. and Argentina, with an average starting weight of 232.4 pounds. Lilly plans to start Phase 3 trials in the fourth quarter of 2026.

What the dose table shows

One detail stands out: eloralintide 6 mg plus only 5 mg of tirzepatide reached 19.4%, more than the top tirzepatide dose on its own. If that holds up in Phase 3, lower doses of each drug could do the job, which matters for tolerability and for manufacturing supply.

The catch in the headline number

The 23.3% uses what Lilly calls the efficacy estimand, which, in the release's words, shows results "had all randomized participants remained on study intervention." The release does not give the treatment-regimen figure, which counts people who stopped, and in this trial many did. Discontinuations due to adverse events ran from 10.8% to 27.0% across the combination arms, against 2.9% for tirzepatide alone and 16.7% for placebo. Lilly did not say which dose had the 27.0% rate.

Lilly said side effects were mostly gastrointestinal, mild to moderate, concentrated in the dose-escalation phase, and more frequent in the combination arms. It plans to run Phase 3 with a co-formulated single product and an "optimized escalation schedule," an admission that the ramp-up used here was too steep. CNBC reported that a Lilly executive pointed to dropout rates of about 25% for tirzepatide's top dose in a 2018 mid-stage trial as evidence that early tolerability numbers improve.

The competitive yardstick is Novo Nordisk's CagriSema, which also pairs an amylin drug with a GLP-1. BioSpace noted that CagriSema produced 23% weight loss at 84 weeks and still lost to Zepbound's 25.5% in a head-to-head study. EloraTZP reached a similar figure in about 57% of that time, though in a different population, since people with diabetes typically lose less weight on these drugs.

Why the stock barely moved

Lilly shares were at $1,185.39 at 10:51 a.m. Eastern, up 0.06% from Tuesday's close, after trading as high as $1,214.99 earlier in the session, according to Nasdaq. Novo Nordisk's U.S. shares were up 1.0% at $38.69. Traders had a second Lilly readout to digest: on Tuesday evening the company reported that retatrutide 12 mg produced 20.8% weight loss over 80 weeks in its Phase 3 TRIUMPH-2 trial in the same kind of patients, and said it plans to file for approval in the first quarter of 2027. Retatrutide is much closer to market, and a mid-stage combination with high dropout rates adds little to near-term revenue estimates.

Sources: Eli Lilly (EloraTZP); Eli Lilly (retatrutide); CNBC; BioSpace; MarketWatch; Nasdaq. Point and time comparisons are our calculations. This is market information, not investment advice.