Novo Nordisk REDEFINE 4 Head-to-Head 84-Week Phase 3 Trial Detail: CagriSema (Cagrilintide 2.4 mg + Semaglutide 2.4 mg Fixed-Dose Combination) Versus Tirzepatide 15 mg in 809 Randomized Adults With Obesity and One or More Comorbidities With Mean Baseline Body Weight of 114.2 kg Documented 23.0% Weight Loss on CagriSema Versus 25.5% on Tirzepatide (Treatment-Policy Estimand) and 20.2% Versus 23.6% (Treatment-Regimen Estimand), Missing the Primary Non-Inferiority Endpoint; CagriSema Safety Profile Was Generally Well-Tolerated; The Trial Result Complicates the Novo Commercial Positioning of CagriSema as Its Tirzepatide-Beating Response Even as the FDA Decision on the Obesity Indication (Filed December 18, 2025 Based on REDEFINE 1 and REDEFINE 2 Pivotal Data) Remains Expected Late 2026
Novo Nordisk released detailed data from the REDEFINE 4 head-to-head 84-week Phase 3 trial of CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg fixed-dose combination) versus tirzepatide 15 mg. Trial design: 809 randomized adults with obesity and one or more comorbidities with mean baseline body weight of 114.2 kg, both drugs administered once weekly subcutaneously over 84 weeks. Primary endpoint results: CagriSema 23.0% weight loss versus tirzepatide 25.5% (treatment-policy estimand); CagriSema 20.2% versus tirzepatide 23.6% (treatment-regimen estimand). The trial missed the primary non-inferiority endpoint on weight loss for CagriSema compared to tirzepatide at 84 weeks. CagriSema safety profile was generally well-tolerated. The trial result complicates the Novo commercial positioning of CagriSema as its tirzepatide-beating differentiated response, though the FDA decision on the CagriSema obesity indication remains expected late 2026 based on the REDEFINE 1 and REDEFINE 2 pivotal trials submitted December 18, 2025. The head-to-head result adds to the widening Lilly-Novo franchise gap: Lilly Q2 2026 Mounjaro + Zepbound reached $14.9 billion in the quarter, while Novo H1 2026 sales reached 78.49 billion Danish kroner ($12.09 billion).