Lilly's 48-week Phase 2 readout hit its main goals and showed the pairing outperformed high-dose tirzepatide alone on weight loss. The top combo dose - 9 milligrams of eloralintide plus 15 milligrams of tirzepatide - produced up to 23.3% average weight loss, roughly 54 pounds. By comparison, participants on tirzepatide 15 milligrams alone lost 14.8% on average, or 34.4 pounds. Eloralintide by itself delivered up to 12.3% average weight loss, or 28.6 pounds.
Glycemic control improved too. The combination cut A1C by as much as 2.9% on average, versus up to 2.4% with higher-dose tirzepatide alone and up to 1.4% with eloralintide alone.
Lilly said these results build on earlier signals: in a Phase 1 study, participants who received 3 milligrams of eloralintide on top of 5 milligrams of tirzepatide saw an average 17% reduction in body weight across 16 weeks in adults with obesity, versus 10% with 5 milligrams of tirzepatide alone.
The regimen marries eloralintide, which targets amylin - a pancreatic hormone that helps regulate appetite and the feeling of fullness - with a reduced amount of tirzepatide, the compound used in Zepbound and Mounjaro. Tirzepatide acts on two gut hormones, GLP-1 and GIP. Lilly's bet: engaging all three pathways may curb hunger more effectively and drive deeper weight loss.
"Patients may not get what they need from a drug like tirzepatide," said Ken Custer, president of Lilly Cardiometabolic Health. "They may not get what they need from a drug like a eloralintide on its own. The ability to combine them together and provide even greater weight loss - that's definitely one obvious" benefit. He added, "This very physiological approach of combining GLP-1, GIP, and amylin, which are three nutrient-stimulated hormones that your body releases naturally in response to food and promotes satiety, putting those things together may just make for a drug that is broadly used." Custer also said the combo could "turn out to be a really winning approach."
As effective as the combo looked, tolerability will be watched closely. Side effects occurred more often in the combination groups than with tirzepatide alone or eloralintide alone. The most common issues were gastrointestinal, generally mild to moderate, and tended to show up when doses were increased.
Stopping treatment due to side effects happened more in the combo arms, ranging from 10.8% to 27% depending on dose, versus 2.9% with tirzepatide alone. Up to 10.8% of people on eloralintide alone discontinued, compared with 16.7% on placebo. Custer urged caution on reading too much into Phase 2 discontinuations, noting the highest tirzepatide dose also saw around 25% discontinuation in a 2018 mid-stage study: "It's probably not the best indicator of the tolerability of a medicine," he told CNBC.
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"We do things in Phase 1 and Phase 2 to test what the molecule can do from an efficacy perspective. We also learn from those studies about how we should administer them, and then we make changes. We do this every time." He said Lilly will refine dosing in Phase 3 and "we expect that we'll end up with a very favorable balance of efficacy and tolerability."
Lilly expects to start Phase 3 on the regimen near the close of the year, and on Wednesday it added that the combo is slated to enter Phase 3 by the end of 2026. The company is developing a co-formulation so patients could get both medicines in a single injection in Phase 3.
The findings were shown at the European Association for the Study of Diabetes meeting in Milan, Italy. Ahead of the readout, some analysts framed Lilly's program as a head-to-head concept with Novo Nordisk's next-wave CagriSema, which brings together amylin and GLP-1 mechanisms. Leerink Partners' David Risinger called eloralintide a "mega-blockbuster" prospect and said it likely has "much greater market potential than the Street currently realized," pointing to "millions" of patients who did not get results on current GLP-1s or could not tolerate them. He also noted the combo could be an alternative to Lilly's other advanced obesity candidate, retatrutide, which targets GLP-1, GIP and glucagon and has delivered some of the highest weight-loss levels seen in trials.
One more note from Lilly's materials: the company pointed to signage at a groundbreaking for its pharmaceutical manufacturing campus located in Generation Park in Houston, Texas, on Monday, Sept. 21, 2026.
If you care about where obesity care is heading, watch two near-term markers: how Lilly tunes dosing in Phase 3 and whether the single-shot co-formulation smooths side effects without giving up efficacy. Those will shape real-world uptake and, eventually, revenues that can move a stock - and shape where new therapies land on your insurance form.
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