Published by Global Banking & Finance Review®
Posted on February 4, 2025
6 min readLast updated: January 26, 2026
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Investors are concerned about Novo Nordisk's CagriSema trial results, which showed lower-than-expected weight loss and side effects, impacting shares.
By Maggie Fick and Robin Respaut
LONDON/SAN FRANCISCO (Reuters) - Novo Nordisk is under pressure from investors for more information about its next-generation obesity drug candidate CagriSema amid a lack of clarity over trial results that hammered its shares in December.
Novo believes CagriSema could be more powerful than its blockbuster weight-loss injection Wegovy, but investors are worried whether it will be good enough to retake the lead from rival Eli Lilly in the competitive obesity drug market.
In interviews with Reuters, five patients who participated in the trial that reported in December - or are part of a separate late-stage study - said the weekly injection helped them shed pounds quickly, but that they encountered what they characterised as significant side-effects including nausea, constipation and fatigue.
In its December read-out, Novo said the most common adverse events in the trial were gastrointestinal and the vast majority were mild to moderate and diminished over time, consistent with CagriSema's broader class of GLP-1 receptor agonist drugs.
Novo declined to comment for this story as it is in the regulatory quiet period ahead of quarterly results on Wednesday.
While anecdotal, the interviews with the five patients shed some light on the experiences of those taking CagriSema and could hint at answers to questions sparked by the data about potential side-effects and the dosing regimen.
Weaker than expected data from the trial was a blow to Novo's ambitions to find a more powerful competitor to Lilly's Zepbound, also known as Mounjaro.
CagriSema combines semaglutide, the active ingredient in Wegovy that mimics gut hormone GLP-1, with a separate molecule called cagrilintide that mimics pancreatic hormone amylin.
One participant in the trial that reported in December said she repeatedly fainted during her first six months on CagriSema. Over the 68-week trial, she lost 29% of her body weight.
"I guess it's quite normal to feel awful when you lose 30 to 40 kilograms in the span of six months," said Jane, who asked to be identified by her middle name to protect her anonymity.
After reaching the highest dose, she stopped losing weight as rapidly. "I got used to it (the medicine). I felt better," she said.
In December, Novo said people who adhered to the CagriSema treatment plan achieved overall weight loss of 22.7% after 68 weeks, with 40.4% losing 25% or more.
That was lower than the 25% across-the-board weight loss it expected. The disappointment wiped as much as $125 billion off Novo's value on the day.
Novo also said only 57.3% of patients reached the highest dose of the medicine, but didn't explain why. Was it because patients suffered side-effects or because they lost weight on lower doses? Both could explain why they didn't progress to the highest dose.
Some investors and analysts were also surprised the trial used a "flexible" protocol, permitting patients to change their dose strength instead of adhering to a schedule.
They said this could be a factor in the low take-up of the highest dose. Novo has said it will start a new trial by June.
IN THE DARK
In interviews with Reuters, more than a dozen investors and analysts called for more clarity about factors they say are weighing on Novo's shares. They hope to get more information at Wednesday's quarterly results.
But Novo may be limited in what it can say as it prepares to release full data and trial protocol at a scientific conference later this year, expected to be the American Diabetes Association meeting in June.
Lukas Leu, fund manager at healthcare-focused Bellevue Asset Management in Switzerland, which holds Novo shares, said he was disappointed Novo did not disclose the flexible dosing earlier or explain its reasons for doing so.
Novo's prior major semaglutide trials permitted participants to stay on lower doses if they experienced "unacceptable side-effects".
In the STEP trial, which studied semaglutide for weight loss, 89.6% of patients completing the trial were receiving the highest dose.
"With CagriSema, people are assuming the worst – on efficacy the drug is not better than Lilly's tirzepatide, on tolerability that it is worse, and that it is harder to manufacture," said Barclays analyst Emily Field, referring to the active ingredient in Lilly's Zepbound/Mounjaro.
"We don't necessarily agree with all those viewpoints, but given lack of additional commentary from the company, I understand why people are taking such a negative approach."
'LIFE CHANGING'
Reuters interviewed two people who participated in the CagriSema trial that reported in December, called REDEFINE-1, and three in an ongoing Phase III trial, called REDEFINE-4, which is testing CagriSema against Zepbound/Mounjaro.
REDEFINE-1 patients did not know until after the trial ended which drug they received. REDEFINE-4 patients know which drug they are getting.
Michelle Rivera, who lives in Dallas, Texas, said she struggled to eat after she began taking CagriSema in the REDEFINE-4 trial.
"Literally nothing was appetising," said Rivera, who has lost about 22% of her weight.
Rivera has taken CagriSema for a year and has six months left on the trial. Her appetite slowly returned after about six months on the drug. But she still eats much smaller portions, prioritising protein, water and fibre to fight constipation.
Her trial investigators were receptive to participants not increasing their dose if side-effects bothered them, she said. She kept to the recommended schedule and reached the maximum dose after about six months.
Another participant in the ongoing trial, Leigh, who asked to be identified by her middle name, said nausea, fatigue and brain fog she experiences in the 24 hours after her weekly CagriSema injection are so bad that she sometimes can't leave bed.
She has, however, kept to the recommended dosing protocol in the hope of losing more weight. After a year on CagriSema, she has lost about 18% of her weight. The medicine is "life changing", she said.
But when she finishes the trial this summer, she wants to explore whether a maintenance dose of a GLP-1 medicine would help her sustain weight loss without such intense side-effects.
"What I'm dealing with now, it's not sustainable," she said.
(Reporting by Maggie Fick in London and Robin Respaut in San Francisco. Editing by Josephine Mason and Mark Potter)
The article discusses investor concerns about Novo Nordisk's obesity drug CagriSema and its trial results.
Investors are worried about the drug's efficacy and side effects compared to competitors like Eli Lilly's Mounjaro.
The trial showed lower-than-expected weight loss and significant side effects, impacting Novo's stock value.
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