Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.
Maria-Ioanna Stefanou, Lina Palaiodimou, Aikaterini Theodorou, Apostolos Safouris, Urs Fischer, Peter J Kelly, Jesse Dawson, Mira Katan, Aristeidis H Katsanos, Vaia Lambadiari, Sotirios Giannopoulos, Andrei V Alexandrov, Gerasimos Siasos, Georgios Tsivgoulis
{"title":"Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.","authors":"Maria-Ioanna Stefanou, Lina Palaiodimou, Aikaterini Theodorou, Apostolos Safouris, Urs Fischer, Peter J Kelly, Jesse Dawson, Mira Katan, Aristeidis H Katsanos, Vaia Lambadiari, Sotirios Giannopoulos, Andrei V Alexandrov, Gerasimos Siasos, Georgios Tsivgoulis","doi":"10.1177/17562864241281903","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.</p><p><strong>Objectives: </strong>The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.</p><p><strong>Data sources and methods: </strong>A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.</p><p><strong>Results: </strong>Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; <i>p</i> < 0.01; <i>I</i> <sup>2</sup> = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; <i>p</i> < 0.01; <i>I</i> <sup>2</sup> = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; <i>p</i> = 0.06; <i>I</i> <sup>2</sup> = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; <i>p</i> < 0.01; <i>I</i> <sup>2</sup> = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; <i>p</i> < 0.01; <i>I</i> <sup>2</sup> = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.</p><p><strong>Conclusion: </strong>GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.</p><p><strong>Trial registration: </strong>PROSPERO CRD42024515966.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437580/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Energy Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864241281903","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.
Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.
Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.
Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; p < 0.01; I2 = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; p < 0.01; I2 = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; p = 0.06; I2 = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; p < 0.01; I2 = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; p < 0.01; I2 = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.
Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.
期刊介绍：
ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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