CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). The combination works by decreasing hunger and increasing the feeling of fullness.
The open-label, randomized REDEFINE 4 trial (ClinicalTrials.gov Identifier: NCT06131437) compared the safety and efficacy of CagriSema with tirzepatide, a glucose-dependent insulinotropic polypeptide receptor and GLP-1RA, in 809 adults with obesity (body mass index [BMI] ≥30kg/m2).
Study participants (mean baseline body weight: 114.2kg) were randomly assigned to receive CagriSema (fixed dose combination of cagrilintide 2.4mg and semaglutide 2.4mg) or tirzepatide 15mg administered subcutaneously once weekly. The primary endpoint was the relative percent change in body weight from baseline to week 84.
Findings showed CagriSema 2.4mg/2.4mg did not meet the noninferiority threshold for weight loss when compared with tirzepatide. Under the efficacy estimand (the effect if all people adhered to the study treatment), patients treated with CagriSema achieved a 23.0% weight loss compared with 25.5% in those treated with tirzepatide. Similarly, when evaluating based on the treatment regimen estimand (treatment effect regardless of treatment adherence), the CagriSema arm achieved a 20.2% weight reduction vs 23.6% in the tirzepatide arm.
The most common adverse events reported with CagriSema were gastrointestinal, though they were mild to moderate in intensity and diminished over time.
“We are pleased with the weight loss of 23% for CagriSema in this open-label trial,” said Martin Holst Lange, executive vice president, R&D and chief scientific officer at Novo Nordisk. “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.”
Novo Nordisk submitted a New Drug Application for CagriSema in weight management in December 2025 based on the REDEFINE 1 and REDEFINE 2 trials. A regulatory decision is expected by late 2026.
References:
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. Novo Nordisk. February 23, 2026. https://www.globenewswire.com/news-release/2026/02/23/3242381/0/en/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.html.
