Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3)

Cagrilintide-semaglutide (CagriSema) is a fixed-dose combination of the amylin receptor agonist cagrilintide and the glucagon-like peptide-1 receptor agonist semaglutide administered subcutaneously once weekly. CagriSema has demonstrated significant weight reduction and improved glycemic control in participants with excess adiposity and type 2 diabetes (T2D).

REDEFINE 3 is a double-blind, randomized, placebo-controlled trial involving participants with established cardiovascular disease (CVD) and body mass index (BMI) ≥25.0 kg/m² with/without T2D randomized to CagriSema 2.4 mg/2.4 mg or placebo, plus standard of care. The safety objective is to confirm noninferiority of CagriSema compared with placebo on cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE-3). The efficacy objective is to confirm the superiority of CagriSema compared with placebo on cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or revascularization (MACE-4).

Between 1/2023-12/2024, 7076 adults at 575 sites in 24 countries were randomized. Mean age at baseline was 66 years. BMI ≥30 kg/m² was present in 76% of participants (n=5370). In participants with T2D (n=4348, 61%), the mean duration of T2D was 12 years and mean glycated hemoglobin was 7.7%. Most participants had a prior myocardial infarction (n=4369, 62%). Prior stroke (n=1311, 19%) and peripheral arterial disease (n=769, 11%) were less common, and 617 participants (9%) had more than one qualifying CVD criteria.

The REDEFINE 3 trial will provide evidence regarding the cardiovascular safety and efficacy of CagriSema, a novel fixed-dose combination therapy that could improve cardiovascular outcomes in a broad population of people with established CVD and excess adiposity.

The REDEFINE 3 trial is registered at ClinicalTrials.gov (NCT05669755).