Key result
REDEFINE 3 trial tests CagriSema versus placebo for MACE in high-risk CVD patients.
Why the study?
The cardiovascular safety and efficacy of the fixed-dose combination CagriSema in people with established cardiovascular disease and excess adiposity was not established.
Does cagrilintide-semaglutide improve cardiovascular outcomes compared with placebo in patients with established cardiovascular disease and excess adiposity?
RCT (n=7,065)
Randomized
Does cagrilintide-semaglutide improve cardiovascular outcomes compared with placebo in patients with established cardiovascular disease and excess adiposity?
The REDEFINE 3 trial will evaluate the cardiovascular safety and efficacy of the novel fixed-dose combination cagrilintide-semaglutide in patients with established CVD and excess adiposity.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The CagriSema data presented at ObesityWeek are very encouraging regarding the effects on well-known CV risk factors like high blood pressure – a strong signal that warrants further investigation. High blood pressure has a significant impact on the heart, increasing the risk of heart attacks and strokes and, alongside inflammation, is a key driver of cardiovascular disease. If we can lower inflammation, bring blood pressure to more normal levels, and help people lose weight at the same time, there's potential for holistic improvement in overall health.”
“We're very excited by the results of these analyses of CagriSema, which show promising results of combining cagrilintide with the proven significant effects of semaglutide on CV health. People living with obesity have treatment goals that often include both losing weight and improving overall health. That's why we continue to explore new therapies that we hope will deliver on weight loss needs while reducing the risk of obesity-related health issues like cardiovascular disease.”
Baseline traits define high-risk cohort for CagriSema CVOT; leaves open dual-agonist effects on MACE.
IMPORTANCE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: The REDEFINE 3 trial is registered at ClinicalTrials.gov (NCT05669755).
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Cavender et al. (2026) conducted an RCT in Cardiovascular disease and excess adiposity with or without type 2 diabetes (n=7,065). Cagrilintide-semaglutide (CagriSema) vs. Placebo was evaluated on Safety: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE-3). Efficacy: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or revascularization (MACE-4). The REDEFINE 3 trial evaluates CagriSema versus placebo for cardiovascular outcomes in patients with established CVD, with baseline data showing 62% of participants had a prior myocardial infarction.
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