Published by Global Banking & Finance Review®
Posted on February 23, 2026
4 min readLast updated: April 2, 2026
Add as preferred source on GoogleIn an 84‑week head‑to‑head, CagriSema missed non‑inferiority to tirzepatide, delivering 23% vs 25.5% weight loss. Novo Nordisk shares fell about 8% on the news.
By Stine Jacobsen and Maggie Fick
COPENHAGEN, Feb 23 (Reuters) - Novo Nordisk's next-generation obesity drug CagriSema underperformed rival Eli Lilly's Zepbound in a head-to-head trial, the Danish drugmaker said on Monday, as it suffered a setback in its fight to regain leadership of the weight-loss market.
Few analysts had predicted CagriSema would be found to be less effective than Lilly's drug that sells as Zepbound in the U.S. and Mounjaro in Europe.
Novo's shares fell 15% to lows not seen since 2021.
The company had positioned CagriSema as a more potent successor to its current weight-loss drug Wegovy that faces patent cliffs after 2030. It hoped it would be a powerful contender to Zepbound as it seeks to regain its market leadership.
"This is a worst-case scenario for Novo, now it is clinically proven that Mounjaro is better than CagriSema," Markus Manns at Novo and Lilly shareholder Union Investment told Reuters, adding Novo now faced an "uphill battle" with the drug.
"The base case was that Mounjaro and CagriSema are similar... Upside was superiority, but nobody had on the agenda, that Cagri would be worse than Mounjaro."
'TO INVESTORS IT'S VERY SIGNIFICANT'
The trial was designed to show CagriSema was at least as effective as tirzepatide in reducing weight. Tirzepatide is sold in the United States under the brand names Zepbound for weight loss and Mounjaro for diabetes, as well as being marketed as Mounjaro in Europe as a treatment for both.
Instead the trial showed CagriSema achieved a 23% reduction in body weight over 84 weeks, compared to 25.5% for Eli Lilly's tirzepatide in the trial, Novo's statement said.
"Weight loss of 23% versus 25.5% after 84 weeks may seem like a minor difference, but to investors it's very significant," said Nordnet's Per Hansen. "In a winner-takes-all world Eli Lilly has cemented its strong momentum."
Lilly's shares rose in pre-market trading.
Henrik Hallengreen Laustsen, analyst at Jyske Bank, called the news a "fairly big setback" for Novo.
"When we look at long-term estimates for Novo, CagriSema makes up a fairly large part of Novo Nordisk's growth," he said, adding that, according to consensus, 60% of Novo's growth will come from CagriSema.
The share price slide means that over $400 billion has been knocked off Novo's market capitalisation since a peak in 2024. That erases the gains after Wegovy's launch in 2021 that made Novo temporarily Europe's most valuable listed firm.
NOVO NORDISK PLANS A HIGH-DOSE TRIAL
CagriSema is a weekly injection combining cagrilintide, which mimics pancreatic hormone amylin, and semaglutide, the active ingredient in Wegovy that mimics the gut hormone GLP-1.
Novo executives sought to strike an optimistic tone in calls with investors and said the drug still had the potential to have "the best weight-loss label" when it launches next year.
Chief Scientific Officer Martin Holst Lange also said the company was "little bit surprised" at Zepbound's performance in the trial.
Analysts were sceptical.
"Without the level of superiority over current high-volume GLP-1s, we believe it is difficult to command a premium positioning for the drug," Jefferies analyst Michael Leuchten wrote in a note.
In the study, Novo tested a fixed-dose combination of cagrilintide 2.4 milligrams and semaglutide 2.4 mg, while patients on tirzepatide received a 15-milligram dose.
The Danish drugmaker plans to start a high-dose trial for CagriSema in the second half of this year.
(Reporting by Stine Jacobsen, Maggie Fick, Bhanvi Satija and Jacob Gronholt-Pedersen; Editing by Terje Solsvik, Adam Jourdan and Barbara Lewis)
Novo Nordisk reported that its obesity drug CagriSema missed the primary endpoint of non‑inferiority to Eli Lilly’s tirzepatide in an 84‑week head‑to‑head trial.
CagriSema achieved 23% body‑weight reduction versus 25.5% for tirzepatide over 84 weeks in the REDEFINE‑4 study, prompting a negative market reaction.
Novo Nordisk shares dropped about 8% intraday. The company continues broader CagriSema studies and may explore higher‑dose combinations as it pursues approvals.
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