On Jun. 22, 2025, The New England Journal of Medicine (NEJM) published results from Novo Nordisk’s phase 3 REDEFINE 1 trial evaluating the efficacy and safety of investigational CagriSema plus lifestyle interventions for weight loss in adults with obesity or overweight who have a weight-related medical complication and without diabetes.

REDEFINE 1 met its co-primary endpoints and achieved statistically significant and clinically meaningful weight loss at 68 weeks in patients taking CagriSema versus placebo. These data, along with the related phase 3 REDEFINE 2 study conducted in adults with overweight or obesity and type 2 diabetes, were published in NEJM.

CagriSema is an investigational product that combines the GLP-1 RA, semaglutide, with an amylin analogue, cagrilintide. The REDEFINE 1 trial found that treatment with CagriSema resulted in greater weight loss of 22.7% at 68 weeks versus 2.3% in the placebo group (estimated difference [95% CI] -20.4 [-21.1 to -19.7]; p<0.001) if all patients adhered to treatment.

When evaluating the treatment effect regardless of adherence, those treated with CagriSema achieved statistically significant weight loss of 20.4% at 68 weeks versus 3.0% for the placebo group (estimated difference [95% CI] -17.3 [-18.1 to -16.6]; p<0.001). In addition, a supportive secondary analysis showed that half (50.7%) of trial participants with obesity treated with CagriSema reached the threshold for non-obesity (BMI <30 kg/m²) at the end of treatment, from a mean BMI of 38 kg/m² at the start of treatment. In the placebo group, 10.2% reached that threshold at 68 weeks.

In REDEFINE 2, if all participants adhered to treatment, the estimated mean change in body weight from baseline to week 68 was -15.7% with CagriSema versus -3.1% with placebo (estimated difference [95% CI] -12.6% [-13.4 to -11.7]; p<0.001). When applying the treatment policy estimand, the estimated mean change in body weight from baseline to week 68 was -13.7% with CagriSema versus -3.4% with placebo (estimated difference [95% CI] -10.4% [-11.2 to -9.5]; p<0.001).

The REDEFINE clinical program will continue to assess the efficacy and safety of CagriSema. Most recently, Novo Nordisk initiated the REDEFINE 11 trial with the first patient visit occurring in early June 2025. REDEFINE 11 will explore further weight loss potential and safety of CagriSema 2.4 mg / 2.4 mg through a longer trial duration and other protocol changes compared to REDEFINE 1 and 2.

CagriSema is being investigated by Novo Nordisk as a once-weekly subcutaneous injectable treatment for adults with overweight or obesity (REDEFINE program) and as a treatment for adults with type 2 diabetes (REIMAGINE program). CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide 2.4 mg and semaglutide 2.4 mg. CagriSema is not approved in the US for weight loss.