CagriSema Fails to Demonstrate Noninferiority to Tirzepatide for Weight Loss: Phase 3 REDEFINE Trial

Topline results from a phase 3 clinical trial compared CagriSema with tirzepatide in patients with obesity. CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a GLP-1 receptor agonist. The therapy promotes weight loss by reducing hunger and enhancing satiety, offering a dual-mechanism approach to appetite control.Findings showed CagriSema 2.4mg/2.4mg did not meet the noninferiority threshold for weight loss when compared with tirzepatide.

When evaluating the effects of treatment, if all people adhered to treatment, people treated with CagriSema 2.4 mg/2.4 mg achieved a weight loss of 23.0% after 84 weeks compared to 25.5% with tirzepatide 15 mg. When applying the treatment-regimen estimand, people treated with CagriSema 2.4 mg/2.4 mg achieved a weight loss of 20.2% compared to 23.6% with tirzepatide at 84 weeks. The trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks.

In the trial, CagriSema appeared to have a safe and well-tolerated profile. The most common adverse events with CagriSema were gastrointestinal, and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class.

“We are pleased with the weight loss of 23% for CagriSema in this open-label trial. 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. Based on the learnings from completed studies we look forward to the REDEFINE 11 readout, and the initiation of the higher-dose CagriSema trial, which are both designed to assess the full weight-loss potential of CagriSema”, said Martin Holst Lange, executive vice president, R&D and chief scientific officer at Novo Nordisk. “The results in the REDEFINE programme reinforce our commitment to transforming obesity care, through novel products such as CagriSema and zenagamtide with the potential to offer even greater health benefits for patients living with obesity.”

CagriSema for weight management was submitted to the US FDA in December 2025 based on the REDEFINE 1 and REDEFINE 2 pivotal trials, and an FDA decision is anticipated by late 2026. The REDEFINE 11 phase 3 trial exploring CagriSema 2.4/2.4 mg full weight-loss potential in obesity is expected to report data during the first half of 2027, while initiation of the phase 3 CagriSema higher-dose trial is planned for the second half of 2026.

About CagriSema

Once-weekly subcutaneous CagriSema is being investigated by Novo Nordisk as a treatment for adults with overweight or obesity (REDEFINE programme) and as a treatment for adults with type 2 diabetes (REIMAGINE programme). CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide 2.4 mg and semaglutide 2.4 mg. The two molecules induce weight loss by reducing hunger, increasing feelings of fullness and thereby help people eat less and reduce their calorie intake.