Novo Nordisk obesity shot tied to greater weight loss at lower doses

CHICAGO - Novo Nordisk A/S’s next-generation obesity shot CagriSema helped patients lose weight in large studies, despite only about three-quarters of the patients ever making it to the highest dose. Surprisingly, patients who chose to stick with a lower dose lost more weight on average.

The studies allowed patients to stop at lower doses of the drug, an unusual option in a trial.

Researchers presenting new data on June 22 at the American Diabetes Association (ADA) meeting in Chicago said the findings offer clues as to how the drug would be used in real life.

There is a group of people who respond very well to this medicine, said Dr Timothy Garvey, director of the Diabetes Research Centre at the University of Alabama at Birmingham, who helped lead the trials.

“Some patients can be really effectively treated” without hitting the highest dose, Dr Garvey said in an interview.

Investigators were allowed to keep people on lower doses to manage side effects or if they were already losing enough weight. It is unclear why some patients did better, though Dr Garvey noted that they tended to have a lower body mass index at the start of the trial. “We need to study that a little more,” he said.

Novo built its next-generation obesity portfolio on CagriSema, which combines its existing blockbuster shot Wegovy with a second, newer medicine. The one-two punch has so far failed to deliver as much weight loss as Novo predicted, taking a toll on the drugmaker’s stock price.

In a study released in December 2024, obese patients lost 20.4 per cent of their weight on CagriSema, short of the company’s oft-touted goal of at least 25 per cent weight loss. A second study in March 2025 on diabetes also failed to deliver as much weight loss as investors had anticipated.

Novo is now presenting full data from both trials as it tries to persuade doctors and investors that the drug can be a contender in the competitive market.

Dr Enrique Caballero, president-elect of medicine and science for the ADA, said the studies showed “very compelling data” for CagriSema.

“It’s a very meaningful weight reduction,” said Dr Caballero, who is also director of international innovation programmes at Harvard Medical School, in an interview. “In competition with the other molecules that are available, that’s really in the ballpark figure of what we are seeing now.”

Novo plans to seek regulatory approval for CagriSema early in 2026, and it is still running a range of large studies to determine just how much the drug can help patients. 

The latest big trial, which began in June, will be longer than the initial studies to capture more potential weight loss, said Dr Martin Holst Lange, Novo’s drug development chief. The company is also testing CagriSema head to head with Eli Lilly & Co’s Zepbound, the obesity drug that is currently winning the majority of new prescriptions in the US.

Among important data being presented this weekend is CagriSema’s safety results, which show the drug cocktail has similar side effects to Wegovy despite delivering more weight loss, Dr Lange said. About 6 per cent of obesity patients and 8.4 per cent of diabetes patients quit the trials due to side effects, dropout rates that Novo said are low.

The drugmaker is also looking to carve out a niche with its drug’s heart benefit. Wegovy is approved to prevent strokes and heart attacks, and Novo is running a large trial to see whether CagriSema can also lead to better outcomes for people with both obesity and heart disease.

Novo is also planning a separate large study of the experimental drug that is mixed with Wegovy to make CagriSema. Called cagrilintide, it mimics a gut hormone called amylin, rather than the GLP-1 hormone that is the basis for Wegovy and Zepbound.

A cagrilintide-only group in the obesity study presented at the ADA meeting lost an average of 11.5 per cent of their body weight. Novo hopes that could create a new market.

“Obviously we need to have the potential for big weight loss for patients who need that, but there will also be patients who need a moderate weight loss,” Dr Lange said. 
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