Le Richard, Nguyen Mau T, Allahwala Momina A, Psaltis James P, Marathe Chinmay S, Marathe Jessica A, Psaltis Peter J
College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia.
Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia.
J Clin Med. 2024 Aug 9;13(16):4674. doi: 10.3390/jcm13164674.
Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.
由于其强大的降糖功效和显著的体重减轻作用,胰高血糖素样肽-1受体激动剂(GLP-1 RAs)现在被认为是治疗2型糖尿病和非糖尿病超重/肥胖的一线治疗选择的一部分。由于在临床结局试验中成功证明了其对心脏代谢的调节作用以及减少主要不良心血管事件,GLP-1 RAs此后已被确认为具有令人信服的心血管保护特性的药物。从基础研究到临床前研究以及大规模随机对照试验的多项研究一直都证实了这类药物的心血管益处。最值得注意的是,越来越多的证据表明它们对动脉粥样硬化性缺血终点有有利影响,临床前数据表明它们可能通过直接改变动脉粥样硬化斑块的负担和成分来实现这一点。这篇叙述性综述探讨了GLP-1 RAs心血管益处背后的潜在药理学和临床证据,特别关注动脉粥样硬化性心血管疾病。它还深入研究了支撑其假定斑块修饰作用的机制,解决了现有的知识空白和治疗挑战,并展望了该领域的未来发展,包括使用联合肠促胰岛素药物进行糖尿病和体重管理。