CagriSema shows substantial weight loss across menopause stages

Menopause-related changes in abdominal fat and body composition can complicate weight management. Two exploratory analyses of REDEFINE 1 suggest substantial weight loss with CagriSema before, during, and after menopause.

The once-weekly injection combines semaglutide, a GLP-1 receptor agonist, with cagrilintide, a long-acting amylin analog that promotes fullness. REDEFINE 1 enrolled adults with obesity or overweight and weight-related complications, without type 2 diabetes.

Among 2,309 women, estimated weight loss at 68 weeks averaged 25.0% with CagriSema versus 19.0% with semaglutide 2.4 mg, 13.4% with cagrilintide, and 3.0% with placebo. These estimates assume participants continued treatment without other weight-loss therapies.

The combination’s additional 6 percentage points of weight loss versus semaglutide could be clinically meaningful. However, greater efficacy than tirzepatide has not been demonstrated: in the separate, open-label REDEFINE 4 trial, adherence-based estimates were 23.0% with CagriSema versus 25.5% with tirzepatide 15 mg at 84 weeks. CagriSema did not meet the trial’s noninferiority endpoint.

Previously reported REIMAGINE 5 results favored lower-dose CagriSema over tirzepatide 5 mg in adults with type 2 diabetes, underscoring that comparisons depend on the doses and populations studied.

In the menopause analysis, estimated losses were 26.7%, 24.8%, and 23.1% in premenopausal, perimenopausal, and postmenopausal women, respectively. Menopause status was assigned retrospectively, and differences in treatment effect between stages were not formally tested.

Tolerability remains relevant. In the overall trial, gastrointestinal adverse events occurred in approximately 80% receiving CagriSema versus 40% receiving placebo. Adverse events prompted discontinuation in 5.9% versus 3.5%.

CagriSema is under FDA review, with a decision expected in the fourth quarter of 2026.

“The weight loss observed in each group is encouraging, and the numerical differences among the groups highlight the need for further research to better understand how reproductive aging may influence weight loss outcomes in women,” said lead author Maria D. Hurtado Andrade, MD, PhD, of Mayo Clinic Alix School of Medicine.

Source: Novo Nordisk. (2026 Oct 20). CagriSema weight-loss analyses from REDEFINE 1 presented at The Menopause Society Annual Meeting