Matthew A Cavender, Ania M Jastreboff, Alice Y Y Cheng, Melanie J Davies, Lucienne Donaldson, Lars-Ole Gerlach, Silas Hinsch Gylvin, Jacob Bonde Jacobsen, Nikolaus Marx, Cynthia Karenina Osorto Contreras, Carel W Le Roux, A Michael Lincoff
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引用次数: 0
Abstract
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: 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).
Results: 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.
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).
期刊介绍：
The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.
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