Elaine Chen , 2025-06-22 13:00:00
CHICAGO — Late-stage results of Novo Nordisk’s obesity candidate CagriSema suggest the drug is comparable to Eli Lilly’s Zepbound on safety and efficacy, further data indicating that CagriSema may not be the standout treatment that investors had hoped for.
Novo previously reported that patients on CagriSema lost 20% of their weight in a 68-week Phase 3 trial when looking at all participants, a similar level of weight loss seen in Zepbound studies.
Novo is planning a longer CagriSema study to see if patients can continue to lose more weight, but full results released Sunday show that the rate of weight loss started to plateau at the end of 68 weeks, raising questions around how much more weight patients would be able to lose.
CagriSema’s tolerability also appeared similar to what’s been observed with Zebpound, according to the study, published in the New England Journal of Medicine and will be presented here at the American Diabetes Association meeting.
About 6% of patients on CagriSema discontinued due to a side effect, a low rate but slightly higher than the 3.5% seen in the placebo group. About 80% of treated patients experienced a gastrointestinal side effect, compared with 40% in the placebo group.
CagriSema and Zepbound “seem fairly equal to me,” said Timothy Garvey, lead investigator of the trial and a professor at the University of Alabama at Birmingham. The difference will ultimately come down to how well the two drugs can treat obesity-related conditions like heart and liver diseases, he added.
Zepbound has a head start since it was developed earlier, with data showing benefits in sleep apnea and heart failure.
CagriSema was originally seen as Novo’s next big blockbuster to come after its popular treatment Wegovy. But the data so far have disappointed investors and led them to view Novo as losing its competitive edge in the obesity drug race.
The CagriSema trial was unique in that it allowed patients to stay on lower doses if they wanted to, which likely contributed to the lower-than-expected efficacy result. It’s still possible that in the longer trial Novo is planning, if more patients end up on the highest dose, there would be greater weight loss, Garvey said.
He stressed, though, that the weight loss seen so far with CagriSema is already significant and more weight loss is not necessarily better. “What the investors want is not what the clinicians want. This is plenty of weight loss,” he said.
Researchers also on Sunday released full results of a second CagriSema trial specifically in patients who have obesity and diabetes. Weight loss was also plateauing at the end of that study.
Across the two CagriSema trials, there were six deaths among patients taking the drug and no deaths in placebo groups. Two deaths were due to suicides, two due to cancer, one due to sudden cardiac death, and one due to other non-cardiovascular causes. None of them were determined to be related to the drug, Garvey said.
The first CagriSema study also measured the body composition changes in about 7% of participants. For treated patients, two-thirds of the weight lost was fat mass and one-third was lean mass. That’s similar to what’s been seen with Zepbound.
Beverly Tchang, an obesity medicine doctor at Weill Cornell Medicine who was not involved in the study, said the flexible dosing design on one hand could be beneficial for real-world use, since it shows insurers that patients don’t have to stay on a fixed dose to lose substantial weight. (Some insurance plans have required patients to titrate up to high doses of obesity medications.)
At the same time, the design could make it harder for some clinicians to decide which dose to keep patients on, she said.
Like Garvey, she sees CagriSema as comparable to Zepbound. “I see them both as equally excellent medications to treat obesity,” she said.
