Head-to-head trial dents Novo Nordisk's obesity hopes

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Mohamed Hassan

Novo Nordisk's new two-drug combination for weight loss, CagriSema, performed worse than Eli Lilly's rival Zepbound in a comparative trial, putting further pressure on its stock.

The Danish pharma group had been hoping to show non-inferiority for CagriSema – combining amylin agonist cagrilintide and GLP-1 agonist semaglutide – compared to dual GP/GLP-1 agonist Zepbound (tirzepatide), which has become a potent competitor to Novo Nordisk's current injectable weight-loss therapy Wegovy (semaglutide) after a head-to-head trial showed it was more effective.

In the open-label REDEFINE 2 trial, CagriSema achieved an average 23% weight loss after 84 weeks of follow-up, which fell short of the 25.5% seen with Lilly's drug. If all patients in the trial were included in the analysis – including those who did not adhere to treatment with the once-weekly injectables – the average weight loss came in at 20.2% with CagriSema and 23.6% with Zepbound.

Novo Nordisk's already-beleaguered shares were down 15% at the time of writing, despite comments from Martin Holst Lange, the company's head of R&D, that he was "pleased" with the result.

The results show "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," he added.

Now, Novo Nordisk is planning to start a trial of a new formulation of CagriSema with a higher dose of semaglutide later this year in the hope of demonstrating the drug's "full weight-loss potential."

CagriSema was submitted for FDA approval last December as a treatment for obesity last December, with a decision due later this year, and Novo Nordisk is also working towards a filing in type 2 diabetes after the drug proved more effective than its Ozempic formulation of semaglutide in a comparative trial.

The filing was made on the back of the REDEFINE 1 and 2 studies, which showed that 40% of people taking CagriSema achieved a body weight reduction of 25%, while 23% lost at least 30%.

The REDEFINE 4 results mean that Novo Nordisk's plans to offer an injectable that can rival the efficacy of Zepbound – sales of which overtook Wegovy in the US in the fourth quarter of 2025 – are now significantly delayed.

It also places even further importance on the Danish company's recently launched oral formulation of Wegovy, which has started well in the US market, but could face competition from Lilly's oral GLP-1 agonist orforglipron within the next few weeks.

Image by Mohamed Hassan from Pixabay