Novo Nordisk Reports REDEFINE 4 Results As CagriSema Shows 23% Weight Loss But Misses Non-Inferiority To Tirzepatide

Novo Nordisk announced headline findings from REDEFINE 4, an 84-week, open-label Phase III trial within its global REDEFINE clinical programme. The study evaluated CagriSema, a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, against tirzepatide 15 mg, both administered once weekly via subcutaneous injection. A total of 809 adults with obesity and at least one weight-related comorbidity were enrolled, with a mean baseline body weight of 114.2 kg.

Under the treatment-adherence analysis, participants receiving CagriSema achieved a mean weight reduction of 23.0% at 84 weeks, compared to 25.5% with tirzepatide. Using the treatment regimen estimand, which accounts for treatment discontinuation and other real-world factors, weight loss reached 20.2% with CagriSema versus 23.6% with tirzepatide. The trial did not meet its primary endpoint of demonstrating non-inferiority of CagriSema compared to tirzepatide for weight reduction at 84 weeks.

“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, demonstrating that cagrilintide adds to the existing benefits of semaglutide and offers clinically meaningful, additive weight-loss effects superior to those 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 demonstrated a safety and tolerability profile consistent with the GLP-1 receptor agonist class. The most frequently reported adverse events were gastrointestinal, predominantly mild to moderate in severity, and generally decreased over time. No unexpected safety findings were reported.

CagriSema for weight management was submitted to the U.S. Food and Drug Administration in December 2025 based on results from the pivotal REDEFINE 1 and REDEFINE 2 trials, with a regulatory decision anticipated by late 2026. Additional development is ongoing, including the REDEFINE 11 Phase III trial, expected to report results in the first half of 2027, and plans to initiate a higher-dose Phase III study in the second half of 2026.