CagriSema beats low-dose tirzepatide for weight loss

Clinical takeaway: CagriSema remains investigational. These trials support potential roles in weight management and type 2 diabetes, but full safety and discontinuation data and separate head-to-head trials against higher tirzepatide doses are needed before its place in therapy can be determined.

CagriSema combines cagrilintide, a long-acting amylin receptor agonist, with the GLP-1 receptor agonist semaglutide in a once-weekly injection. Company-reported topline results from two Novo Nordisk–sponsored phase 3 trials suggest that CagriSema 1 mg/1 mg may produce substantial weight loss while maintaining strong glycemic efficacy.

In the randomized, open-label REIMAGINE 5 trial, 1,023 adults with type 2 diabetes inadequately controlled with metformin, an SGLT2 inhibitor, or both received CagriSema 1 mg/1 mg or tirzepatide 5 mg. At week 60, average weight loss was 12.4% with CagriSema versus 9.1% with tirzepatide, meeting the superiority endpoint. A1c declined by 1.71 and 1.67 percentage points, respectively, establishing noninferiority.

The comparison should be interpreted narrowly: the trial evaluated only tirzepatide 5 mg, so it cannot show how CagriSema compares with higher tirzepatide doses used in practice.

In the separate REDEFINE 9 trial, 300 adults with overweight or obesity were randomized to CagriSema 1 mg/1 mg, CagriSema 1.7 mg/1.7 mg, or placebo, alongside diet and physical activity. At week 68, participants receiving CagriSema 1 mg/1 mg lost an estimated 21% of body weight, compared with 2% with placebo. Systolic blood pressure, waist-to-height ratio, and fasting lipid levels improved more than with placebo, although numerical results were not provided. Results for the 1.7 mg/1.7 mg group and the proportion achieving at least 5% weight loss were not disclosed.

Novo Nordisk said CagriSema was generally well tolerated, with safety findings consistent with previous studies, but detailed adverse event, serious adverse event, and discontinuation data were not released. The findings remain company-reported topline results and have not been presented in full or peer reviewed.

The manufacturer submitted CagriSema to FDA for a weight management indication in December 2025 and expects a decision in the fourth quarter of 2026.

Source: Novo Nordisk. (2026 Sep 21). Novo’s CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial