Role of Incretin Mimetics in Cardiovascular Outcomes and Other Classical Cardiovascular Risk Factors beyond Obesity and Diabetes Mellitus in Nondiabetic Adults with Obesity: a Meta-analysis of Randomized Controlled Trials

IF 2.8 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

American Journal of Cardiovascular Drugs Pub Date : 2024-11-30 DOI:10.1007/s40256-024-00695-9

William Kamarullah, Raymond Pranata, Siska Wiramihardja, Badai Bhatara Tiksnadi

{"title":"Role of Incretin Mimetics in Cardiovascular Outcomes and Other Classical Cardiovascular Risk Factors beyond Obesity and Diabetes Mellitus in Nondiabetic Adults with Obesity: a Meta-analysis of Randomized Controlled Trials","authors":"William Kamarullah, Raymond Pranata, Siska Wiramihardja, Badai Bhatara Tiksnadi","doi":"10.1007/s40256-024-00695-9","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Emerging data on cardiovascular outcomes, specifically major adverse cardiovascular events (MACE), are being reported from various trials involving incretin mimetics, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and glucose-dependent insulinotropic polypeptide (GIP), especially among patients with obesity and diabetes. Our aim was to evaluate this matter, while also involving various traditional cardiovascular risk factors [e.g., several body weight (BW) parameters, blood pressure (BP), lipid profile].</p><h3>Methods</h3><p>A search of PubMed, Europe PMC, ScienceDirect, Cochrane, and ClinicalTrials.gov up to September 2024 was performed to identify GLP-1 RA and GIP trials in MACE risk reduction as a primary endpoint. Our secondary endpoints included a reduction in BW, waist circumference (WC), body mass index (BMI), BP changes, and lipid modifying effects, while also yielding safety concerns surrounding the use of these pharmaceutical agents. Mean differences (MD) and risk ratios (RR) were summarized using random-effects model.</p><h3>Results</h3><p>A total of 11 eligible randomized controlled trials (RCTs) comprising 8 GLP-1 RA trials and 3 dual GLP-1 RA/GIP (tirzepatide) trials were included. Compared with control groups, GLP-1 RA significantly reduced the MACE risk by 32% [RR 0.68 (95% CI 0.53–0.87); <i>P</i> = 0.002; <i>I</i><sup>2</sup> = 73%, <i>P</i>-heterogeneity < 0.001] and 59% for tirzepatide [RR 0.41 (95% CI 0.18–0.92); <i>P</i> = 0.03; <i>I</i><sup>2</sup> = 0%, <i>P</i>-heterogeneity = 0.96]. Incretin mimetics also substantially reduced BW, BP, and improved lipid panel measures. However, there was an increased risk of adverse events, specifically gastrointestinal disorders within the incretin mimetics subset.</p><h3>Conclusions</h3><p>Incretin mimetics have shown promise in reducing MACE risk while also enhancing cardiovascular risk factors, including blood pressure and lipid profile, in adults with obesity without diabetes.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"25 2","pages":"203 - 229"},"PeriodicalIF":2.8000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Cardiovascular Drugs","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40256-024-00695-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Emerging data on cardiovascular outcomes, specifically major adverse cardiovascular events (MACE), are being reported from various trials involving incretin mimetics, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and glucose-dependent insulinotropic polypeptide (GIP), especially among patients with obesity and diabetes. Our aim was to evaluate this matter, while also involving various traditional cardiovascular risk factors [e.g., several body weight (BW) parameters, blood pressure (BP), lipid profile].

Methods

A search of PubMed, Europe PMC, ScienceDirect, Cochrane, and ClinicalTrials.gov up to September 2024 was performed to identify GLP-1 RA and GIP trials in MACE risk reduction as a primary endpoint. Our secondary endpoints included a reduction in BW, waist circumference (WC), body mass index (BMI), BP changes, and lipid modifying effects, while also yielding safety concerns surrounding the use of these pharmaceutical agents. Mean differences (MD) and risk ratios (RR) were summarized using random-effects model.

Results

A total of 11 eligible randomized controlled trials (RCTs) comprising 8 GLP-1 RA trials and 3 dual GLP-1 RA/GIP (tirzepatide) trials were included. Compared with control groups, GLP-1 RA significantly reduced the MACE risk by 32% [RR 0.68 (95% CI 0.53–0.87); P = 0.002; I² = 73%, P-heterogeneity < 0.001] and 59% for tirzepatide [RR 0.41 (95% CI 0.18–0.92); P = 0.03; I² = 0%, P-heterogeneity = 0.96]. Incretin mimetics also substantially reduced BW, BP, and improved lipid panel measures. However, there was an increased risk of adverse events, specifically gastrointestinal disorders within the incretin mimetics subset.

Conclusions

Incretin mimetics have shown promise in reducing MACE risk while also enhancing cardiovascular risk factors, including blood pressure and lipid profile, in adults with obesity without diabetes.

查看原文本刊更多论文

肠促胰岛素模拟物在非糖尿病成人肥胖患者心血管结局和其他经典心血管危险因素中的作用：一项随机对照试验的荟萃分析

背景：关于心血管结局的新数据，特别是主要不良心血管事件（MACE），正在从各种涉及肠促胰岛素模拟物的试验中报道，如胰高血糖素样肽-1受体激动剂（GLP-1 RA）和葡萄糖依赖性胰岛素性多肽（GIP），特别是在肥胖和糖尿病患者中。我们的目的是评估这一问题，同时也涉及各种传统的心血管危险因素[例如，几个体重（BW）参数，血压（BP），血脂]。方法：检索PubMed， Europe PMC, ScienceDirect， Cochrane和ClinicalTrials.gov，直到2024年9月，确定GLP-1 RA和GIP试验将MACE风险降低作为主要终点。我们的次要终点包括体重、腰围（WC）、体重指数（BMI）、血压变化和脂质修饰作用的降低，同时也产生了使用这些药物的安全性问题。采用随机效应模型总结平均差异（MD）和风险比（RR）。结果：共纳入11项符合条件的随机对照试验（rct），包括8项GLP-1 RA试验和3项GLP-1 RA/GIP（替西肽）双试验。与对照组相比，GLP-1 RA显著降低MACE风险32% [RR 0.68 (95% CI 0.53-0.87)；P = 0.002；I2 = 73%， p异质性< 0.001]，替西帕肽为59% [RR 0.41 (95% CI 0.18-0.92)；P = 0.03；I2 = 0%， p异质性= 0.96]。肠促胰岛素模拟物也能显著降低体重、血压，并改善脂质面板测量。然而，有不良事件的风险增加，特别是胃肠道疾病在肠促胰岛素模拟亚群。结论：模拟肠促胰岛素已显示出降低MACE风险的希望，同时也增加心血管危险因素，包括血压和血脂，成人肥胖无糖尿病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

American Journal of Cardiovascular Drugs 医学-心血管系统

CiteScore

6.70

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents. Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations. The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.