Novo Nordisk has released headline results from the REDEFINE 4 Phase III trial, evaluating its next-generation weight-loss candidate, CagriSema, against Eli Lilly's tirzepatide (Zepbound/Mounjaro).
REDEFINE 4 was an 84-week, open-label phase 3 study comparing CagriSema—a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg—against tirzepatide 15 mg, both administered once weekly via injection. The trial enrolled 809 participants with obesity and at least one comorbidity, with an average starting weight of 114.2 kg.
Results showed that among participants who adhered fully to treatment, CagriSema produced a 23% weight loss at 84 weeks, versus 25.5% for tirzepatide. Using a treatment-regimen analysis, weight loss was 20.2% with CagriSema and 23.6% with tirzepatide. The trial did not meet its primary endpoint of proving non-inferiority for CagriSema relative to tirzepatide.
CagriSema’s safety profile appeared favorable, with most adverse events being gastrointestinal, mild to moderate, and diminishing over time—consistent with expectations for GLP-1 receptor agonists.
“We are pleased with the weight loss of 23% for CagriSema in this open-label trial. CagriSema has the potential to be the first GLP-1/amylin-combination product to reach the market for people living with obesity, documenting 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.
"Based on the learnings from completed studies we look forward to the REDEFINE 11 readout, and the initiation of the higher-dose CagriSema trial, which are both designed to assess the full weight-loss potential of CagriSema,” said Martin Holst Lange, executive vice president, R&D and chief scientific officer at Novo Nordisk.
"The results in the REDEFINE programme reinforce our commitment to transforming obesity care, through novel products such as CagriSema and zenagamtide with the potential to offer even greater health benefits for patients living with obesity.”
CagriSema for weight management was submitted to the US FDA in December 2025, based on the REDEFINE 1 and 2 pivotal trials, with a decision expected by late 2026. The REDEFINE 11 trial, which will assess CagriSema’s full weight-loss potential, is slated to report data in the first half of 2027, while a higher-dose phase 3 trial is planned for the second half of 2026.
