Novo Nordisk (NVO) shares fell nearly 11% in premarket trading Monday after the company’s next-generation obesity drug CagriSema delivered less weight loss than Eli Lilly’s (LLY) competing treatment in a phase 3 trial, raising new concerns about its sales potential.
The REDEFINE 4 trial included 809 randomized people with obesity and one or more comorbidities and with a mean baseline body weight of 114.2 kg. It investigated CagriSema (a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg) compared to tirzepatide 15 mg, both administered once-weekly and subcutaneously.
Patients taking a standard dose of CagriSema lost 20.2% of their body weight after 84 weeks, compared with 23.6% for Lilly’s tirzepatide. “The trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks,” Novo said.
Lilly (LLY) shares rose as much as 4.2% in U.S. premarket trading following the results.
CagriSema is considered a key part of Novo’s strategy as it faces intensifying competition and future patent expirations for its blockbuster drugs Wegovy and Ozempic. The once-weekly subcutaneous therapy is being investigated by Novo Nordisk as a treatment for adults with overweight or obesity (REDEFINE program) and as a treatment for adults with type 2 diabetes (REIMAGINE program).
The therapy combines semaglutide with a compound that mimics the gut hormone amylin, but results have been mixed, including a prior obesity study that missed Novo’s weight-loss target. Analysts had expected the drug to at least match tirzepatide’s performance.
CagriSema for weight management was submitted to the US FDA in December 2025 based on the REDEFINE 1 and REDEFINE 2 pivotal trials, and an FDA decision is anticipated by late 2026.