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Background: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). Results: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD − 4.76 mmHg; 95% CI − 6.03, − 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD − 1.41 mmHg; 95% CI − 2.64, − 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). Conclusions: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis. Registration: PROSPERO identifier number CRD42023475226. [ABSTRACT FROM AUTHOR]