From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Søborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.).
N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11.
Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.
In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed.
A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).
In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).
胰高血糖素样肽-1 受体激动剂司美格鲁肽已被证明可降低糖尿病患者发生不良心血管事件的风险。在不患有糖尿病的情况下，司美格鲁肽是否可以降低超重和肥胖相关的心血管风险尚不清楚。
在一项多中心、双盲、随机、安慰剂对照、事件驱动的优效性试验中，我们纳入了年龄在 45 岁及以上、既往患有心血管疾病且身体质量指数（体重以千克为单位除以身高以米为单位的平方）≥27 但无糖尿病病史的患者。患者以 1:1 的比例随机分配，接受每周一次皮下注射 2.4mg 司美格鲁肽或安慰剂。主要心血管终点是首次发生心血管死亡、非致死性心肌梗死或非致死性卒中的复合事件，采用时间至首次事件分析。同时评估安全性。
共纳入 17604 例患者；8803 例患者被分配接受司美格鲁肽治疗，8801 例患者接受安慰剂治疗。司美格鲁肽或安慰剂暴露的平均（±SD）持续时间为 34.2±13.7 个月，平均随访时间为 39.8±9.4 个月。在司美格鲁肽组 8803 例患者中有 569 例（6.5%）和安慰剂组 8801 例患者中有 701 例（8.0%）发生主要心血管终点事件（风险比，0.80；95%置信区间，0.72 至 0.90；P<0.001）。司美格鲁肽组有 1461 例（16.6%）患者和安慰剂组有 718 例（8.2%）患者因不良事件导致试验药物永久停药（P<0.001）。
在患有既往心血管疾病且超重或肥胖但无糖尿病的患者中，与安慰剂相比，每周皮下注射 2.4mg 司美格鲁肽可降低心血管原因导致的死亡、非致死性心肌梗死或非致死性卒中的发生率，平均随访 39.8 个月。（由 Novo Nordisk 资助；SELECT 临床试验.gov 编号，NCT03574597.）。
