胰高血糖素样肽-1受体激动剂在心力衰竭中的心脏保护作用:神话还是事实?

Cardioprotective effects of glucagon-like peptide 1 receptor agonists in heart failure: Myth or truth?

作者信息

Nesti Lorenzo, Trico Domenico

机构信息

Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.

Laboratory of Metabolism, Nutrition, and Atherosclerosis, University of Pisa, Pisa 56126, Italy.

出版信息

World J Diabetes. 2024 May 15;15(5):818-822. doi: 10.4239/wjd.v15.i5.818.

Abstract

Therapy with glucagon-like peptide 1 (GLP1) receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes. However, while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect, controversies remain on its impact on heart failure. GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction (as demonstrated by the recent STEP-HFpEF Trial). Still, GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction (the LIVE trial). GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects (improved weight management, glycemic control, blood pressure, systemic and tissue inflammation), while direct effects on the heart have been questioned. Nonetheless, weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions. Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide, representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits. Whether this class of therapies is going to change the history of heart failure is an ongoing debate.

摘要

胰高血糖素样肽1(GLP1)受体激动剂疗法因其在预防动脉粥样硬化和心力衰竭相关结局方面的有益心血管作用而引起了极大关注。然而,虽然关于动脉粥样硬化的证据一致表明其具有类效应的心脏保护潜力,但关于其对心力衰竭的影响仍存在争议。GLP1受体激动剂似乎可预防新发心力衰竭的住院治疗,并减轻射血分数保留的心力衰竭患者的症状(最近的STEP-HFpEF试验已证明)。尽管如此,GLP1激动剂对射血分数降低的已确诊心力衰竭患者产生了中性甚至有害的影响(LIVE试验)。GLP1受体激动剂通过其显著的代谢作用(改善体重管理、血糖控制、血压、全身和组织炎症)间接有益于心血管系统,而其对心脏的直接作用受到质疑。尽管如此,通过GLP1受体激动剂单独实现的体重减轻未能改善左心室功能。替尔泊肽是GLP1和葡萄糖依赖性促胰岛素多肽的双重激动剂,是糖尿病治疗中的一种创新选择,对体重减轻有重大影响,并有望带来心血管益处。这类疗法是否会改变心力衰竭的历史仍在持续争论中。

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