Novo Nordisk’s GLP-1/amylin combo has failed to beat Eli Lilly’s obesity blockbuster Zepbound in a phase 3 weight loss study, further denting the Danish pharma’s attempts to reclaim its obesity crown.
The highly anticipated open-label study of 809 people with obesity put a once-weekly shot of Novo’s CagriSema—which combines Wegovy’s ingredient semaglutide with the experimental amylin receptor agonist cagrilintide—up against Zepbound’s ingredient tirzepatide. Novo’s next-gen obesity asset came out worse.
Over 84 weeks, the 2.4/2.4-mg dose of CagriSema was tied to 23% weight loss. Meanwhile, a 15-mg weekly dose of tirzepatide achieved weight loss of 25.5%, according to the Feb. 23 release.
The poor showing against Zepbound is a major blow for Novo’s next-gen obesity treatment plans. The pharma already submitted an approval application to the FDA in December for CagriSema for weight loss, and, earlier this month, the company showed the GLP-1/amylin combo beat Wegovy when it came to weight loss among patients with diabetes.
Novo Chief Scientific Officer Martin Holst Lange, M.D., Ph.D., tried to put a brave face on this morning’s phase 3 failure, claiming the company was “pleased with the weight loss of 23% for CagriSema.”
“CagriSema has the potential to be the first GLP-1/amylin-combination product to reach the market for people living with obesity, documenting that cagrilintide adds to the existing benefits of semaglutide and offers clinically meaningful additive weight loss effects superior to what has been observed with GLP-1 biology alone,” Holst Lange said in a statement.
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The CSO attempted to look ahead to other CagriSema trials in the Redefine series. He singled out a phase 3 obesity study of CagriSema against placebo, which is expected to read out in the first half of next year, as well as the launch of a higher-dose CagriSema trial, which is penciled in for the second half of 2026.
“The results in the Redefine programme reinforce our commitment to transforming obesity care, through novel products such as CagriSema and zenagamtide with the potential to offer even greater health benefits for patients living with obesity,” Holst Lange added.
Investors didn’t seem as reassured by his positive outlook, sending Novo’s share price down 15% to $39.90 in Monday premarket trading on the Nasdaq from a Friday closing price of $47.42. In contrast, Lilly’s stock was up a more modest 3.5% to $1,044.98.
The gaping chasm between the two obesity leaders’ share price is a reminder of how far Novo has fallen behind. Last year saw the company lay off 9,000 employees and bring in a new CEO in an attempt to refocus the Danish pharma after disappointing U.S. sales of Wegovy.
This year got off to a better start, with the launch of a Wegovy pill making Novo the first to market with an oral GLP-1. But this morning’s phase 3 fail for CagriSema raises doubts about a key pillar in Novo’s next-gen obesity strategy.
On an earnings call earlier this month, Novo CEO Maziar Mike Doustdar explained to journalists that while showing noninferiority against tirzepatide was the company’s “base expectation,” the “outside case will be superiority.” In the end, CagriSema was unable to reach either objective.
Beyond CagriSema, Novo’s other weight loss bets included cagrilintide as a monotherapy, which entered phase 3 last year, and zenagamtide, the new name for the dual GLP-1 and amylin agonist amycretin, which is due to enter a late-stage study in the first half of 2026. There’s also UBT251, a triple agonist for GLP-1, GIP and glucagon, which recently began a phase 1b/ 2 trial.
