Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data.

IF 2 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Current Opinion in Cardiology Pub Date : 2023-11-01 Epub Date: 2023-08-21 DOI:10.1097/HCO.0000000000001084

Ronald M Goldenberg, Hwee Teoh, Subodh Verma

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引用次数: 0

Abstract

Purpose of review: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of type 2 diabetes (T2D) and obesity, and some are recommended for cardiorenal risk reduction in T2D. To enhance the benefits with GLP-RA mono-agonist therapy, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists are in development to capitalize on the synergism of GLP-1 and GIP agonism. We review the mechanisms of action and clinical data for GLP-1/GIP receptor co-agonists in T2D and obesity and their potential role in cardiovascular protection.

Recent findings: Tirzepatide, a first-in-class unimolecular GLP-1/GIP receptor co-agonist, is approved for T2D and is awaiting approval for obesity management. Phase 3 trials in T2D cohorts revealed significant reductions in glycemia and body weight and superiority compared with GLP-1R mono-agonism with semaglutide. Tirzepatide has demonstrated significant body weight reductions in individuals with obesity but not diabetes. It enhances lipid metabolism, reduces blood pressure, and lowers liver fat content. Pooled phase 2/3 data showed cardiovascular safety in T2D while a post hoc analysis suggested tirzepatide slows the decline of kidney function in T2D.

Summary: GLP-1/GIP receptor co-agonists are a novel addition to the diabetes and obesity armamentarium. The cardiorenal-metabolic benefits position them as promising multiprong tools for metabolically complex individuals with chronic vascular complications.

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胰高血糖素样肽-1/葡萄糖依赖性促胰岛素多肽受体共激动剂对心脏保护、2型糖尿病和肥胖的作用：机制和临床数据综述。

综述目的：胰高血糖素样肽-1受体激动剂（GLP-1RA）已被批准用于治疗2型糖尿病（T2D）和肥胖，其中一些被推荐用于降低T2D的心肾风险。为了增强GLP-RA单激动剂治疗的益处，GLP-1/葡萄糖依赖性促胰岛素多肽（GIP）受体共激动剂正在开发中，以利用GLP-1和GIP激动剂的协同作用。我们综述了GLP-1/GIP受体共激动剂在T2D和肥胖中的作用机制和临床数据，以及它们在心血管保护中的潜在作用。最近的发现：替西帕肽是第一种单分子GLP-1/GIP受体共激动剂，已被批准用于T2D，目前正在等待肥胖治疗的批准。T2D队列的3期试验显示，与使用西格鲁肽的GLP-1R单激动剂相比，血糖和体重显著降低，并具有优越性。Tirzepatide已经证明肥胖但糖尿病患者的体重显著减轻。它能增强脂质代谢，降低血压，降低肝脏脂肪含量。合并的2/3期数据显示T2D患者的心血管安全性，而一项事后分析表明，替西帕肽可减缓T2D患者肾功能的下降。总结：GLP-1/GIP受体共激动剂是糖尿病和肥胖药物的一种新添加。心肾代谢益处使其成为代谢复杂的慢性血管并发症患者的有前途的多功能工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Cardiology 医学-心血管系统

CiteScore

4.20

自引率

4.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Cardiology is a bimonthly publication offering a unique and wide ranging perspective on the key developments in the field. Each issue features hand-picked review articles from our team of expert editors. With fourteen disciplines published across the year – including arrhythmias, molecular genetics, HDL cholesterol and clinical trials – every issue also contains annotated reference detailing the merits of the most important papers.