Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials

ABSTRACT Background The cardioprotective effects of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)‐based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta‐analysis evaluates their impact on cardiovascular events and metabolic parameters in this popul...

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Main Authors: Yue Yin, Minghan Zhang, Qiuyu Cao, Lin Lin, Jieli Lu, Yufang Bi, Yuhong Chen
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Journal of Diabetes
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Online Access:https://doi.org/10.1111/1753-0407.70082
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author Yue Yin
Minghan Zhang
Qiuyu Cao
Lin Lin
Jieli Lu
Yufang Bi
Yuhong Chen
author_facet Yue Yin
Minghan Zhang
Qiuyu Cao
Lin Lin
Jieli Lu
Yufang Bi
Yuhong Chen
author_sort Yue Yin
collection DOAJ
description ABSTRACT Background The cardioprotective effects of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)‐based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta‐analysis evaluates their impact on cardiovascular events and metabolic parameters in this population. Methods A meta‐analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP‐1RA‐based therapies with placebo and reported cardiovascular events and metabolic parameters. Results A total of 29 RCTs involving 9 GLP‐1RA‐based drugs and 37 348 eligible participants were included. Compared to placebo, GLP‐1RA‐based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all‐cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP‐1RA‐based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP‐1RA‐based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: −7.10 mmHg, 95% CI: [−11.00, −2.70]). Tirzepatide induced the greatest reduction in body mass index (−6.50 kg/m2, [−7.90, −5.10]) and hemoglobin A1c concentrations (−0.39%, [−0.52, −0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C‐reactive protein levels (−1.20 mg/dL, [−1.80, −0.63]), respectively. Conclusions In nondiabetic individuals with overweight or obesity, GLP‐1RA‐based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP‐1RA‐based therapies targeting cardiovascular risk factors.
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spelling doaj-art-e94d2d026ba14daaa78f09542e3d66e32025-08-20T02:30:06ZengWileyJournal of Diabetes1753-03931753-04072025-04-01174n/an/a10.1111/1753-0407.70082Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled TrialsYue Yin0Minghan Zhang1Qiuyu Cao2Lin Lin3Jieli Lu4Yufang Bi5Yuhong Chen6Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine Ruijin Hospital, Shanghai JiaoTong University School of Medicine Shanghai ChinaABSTRACT Background The cardioprotective effects of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)‐based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta‐analysis evaluates their impact on cardiovascular events and metabolic parameters in this population. Methods A meta‐analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP‐1RA‐based therapies with placebo and reported cardiovascular events and metabolic parameters. Results A total of 29 RCTs involving 9 GLP‐1RA‐based drugs and 37 348 eligible participants were included. Compared to placebo, GLP‐1RA‐based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all‐cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP‐1RA‐based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP‐1RA‐based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: −7.10 mmHg, 95% CI: [−11.00, −2.70]). Tirzepatide induced the greatest reduction in body mass index (−6.50 kg/m2, [−7.90, −5.10]) and hemoglobin A1c concentrations (−0.39%, [−0.52, −0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C‐reactive protein levels (−1.20 mg/dL, [−1.80, −0.63]), respectively. Conclusions In nondiabetic individuals with overweight or obesity, GLP‐1RA‐based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP‐1RA‐based therapies targeting cardiovascular risk factors.https://doi.org/10.1111/1753-0407.70082cardiometaboliccardiovascular diseaseGLP‐1 receptor agonist‐based therapiesGLP‐1RAsmeta‐analysisobesity or overweight
spellingShingle Yue Yin
Minghan Zhang
Qiuyu Cao
Lin Lin
Jieli Lu
Yufang Bi
Yuhong Chen
Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
Journal of Diabetes
cardiometabolic
cardiovascular disease
GLP‐1 receptor agonist‐based therapies
GLP‐1RAs
meta‐analysis
obesity or overweight
title Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
title_full Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
title_fullStr Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
title_full_unstemmed Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
title_short Efficacy of GLP‐1 Receptor Agonist‐Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta‐Analysis of Randomized Controlled Trials
title_sort efficacy of glp 1 receptor agonist based therapies on cardiovascular events and cardiometabolic parameters in obese individuals without diabetes a meta analysis of randomized controlled trials
topic cardiometabolic
cardiovascular disease
GLP‐1 receptor agonist‐based therapies
GLP‐1RAs
meta‐analysis
obesity or overweight
url https://doi.org/10.1111/1753-0407.70082
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