FDA
CagriSema delivers 23% weight loss but misses primary endpoint in REDEFINE 4 trial
Novo Nordisk’s REDEFINE 4 trial (NCT06131437) evaluated the fixed‑dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg against tirzepatide 15 mg in 809 adults with obesity and at least one comorbidity. The company reported that participants receiving CagriSema achieved 23.0% mean weight loss at 84 weeks, compared with 25.5% for tirzepatide under the efficacy estimand. Under the treatment‑regimen estimand, weight loss was 20.2% with CagriSema vs. 23.6% with tirzepatide. As a result, the trial did not meet its primary endpoint of demonstrating non‑inferiority for percent weight loss at week 84. CagriSema’s safety profile was consistent with GLP‑1‑based therapy, with GI adverse events mostly mild to moderate and decreasing over time.
Clinical takeaway: For clinicians navigating obesity‑treatment options, CagriSema shows meaningful weight‑loss potential but currently trails tirzepatide; ongoing trials with higher‑dose regimens may clarify whether its additive GLP‑1/amylin mechanism can deliver competitive advantages.
Source:
Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. [News release]. 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916501