Eli Lilly's Eloralintide and Tirzepatide Combo Delivers Up to 23.3% Weight Loss in Phase 2, Beating Tirzepatide Alone

LLY said on Wednesday that pairing its experimental amylin drug eloralintide with tirzepatide, the active ingredient in Zepbound and Mounjaro, produced more weight loss than high-dose tirzepatide alone in a 48-week Phase 2 trial of people with obesity and type 2 diabetes. At the highest combination dose, 9 mg of eloralintide plus 15 mg of tirzepatide, patients lost up to 23.3% of their body weight on average, or about 54 pounds, compared with 14.8% for 15 mg of tirzepatide alone and up to 12.3% for eloralintide alone. The results were presented at the European Association for the Study of Diabetes meeting in Milan, and Lilly plans to move the regimen into Phase 3 by the end of 2026, including a co-formulation that would put both drugs in a single injection.

The combination also lowered A1C, a key blood sugar measure, by up to 2.9% on average, versus up to 2.4% for higher-dose tirzepatide and up to 1.4% for eloralintide alone. Tolerability is the open question: 10.8% to 27% of patients on the combination discontinued because of side effects, depending on dose, compared with 2.9% on tirzepatide alone and 16.7% on placebo. The side effects were mostly gastrointestinal, generally mild or moderate, and clustered around dose increases. Ken Custer, president of Lilly Cardiometabolic Health, pointed out that the highest tirzepatide dose showed discontinuation of around 25% in its own mid-stage trial in 2018, and said Lilly will adjust dosing in Phase 3.

The readout sets up a direct comparison with NVO's CagriSema, which also combines amylin and GLP-1 activity. Ahead of the data, Leerink Partners analyst David Risinger said he sees "mega-blockbuster" sales potential for eloralintide. A day earlier, Lilly also released an indirect analysis finding that Zepbound 15 mg and 10 mg delivered 4.5 and 3.2 percentage points more weight loss over 72 weeks than high-dose Wegovy, although that comparison pooled Lilly's SURMOUNT-1 study with Novo's STEP UP studies rather than testing the drugs head to head.

What to watch: whether the Phase 3 dosing changes bring discontinuation rates closer to tirzepatide alone, how the single-injection co-formulation performs, and how the regimen is positioned against Lilly's own retatrutide and Novo's CagriSema as the obesity market moves to multi-hormone treatments.