Cardiovascular Outcomes of GLP‐1–Based Medicines Among People With Overweight and Obesity: An Umbrella Review of Meta‐Analyses of Randomized Controlled Trials

INTRODUCTION: Cardiovascular (CV) outcomes of Glucagon-like peptide-1 (GLP-1)-based medicines among people with overweight and obese (OW/OB) population have been investigated by meta-analyses of randomized controlled trials (RCTs), but an overall summary is lacking. METHODS: PubMed, EMBASE, Epistemonikos, and Cochrane databases were searched till May 2024 for meta-analyses of RCTs that assessed CV outcomes of GLP-1-based medicines among people with OW/OB. GRADE approach was used to assess strength of associations. RESULTS: Nine studies with 58 unique meta-analyses were included. Fifteen (25.9%) associations were statistically significant. Five high certainty evidence demonstrated beneficial effects of GLP-1 RAs on any CV events (N= 1), major adverse cardiac events (MACE) (N = 2), and myocardial infarction (MI) (N = 2), whereas two associations on revascularization (N = 1) and CV events (N = 1) were supported by moderate certainty. Four associations demonstrated inverse effects of tirzepatide on MACE (N = 1; moderate) and hypertension (N = 3; low). Remaining four demonstrated higher risk of arrhythmia with GLP-1 RAs (N = 1; moderate) and increased heart rate with tirzepatide (N = 3; low to moderate). Although the inverse association between GLP-1 RAs and MACE and MI was significant and supported by high certainty evidence in both main and sensitivity analyses, these associations were no longer statistically significant among patients without CV disease (CVD) at baseline. CONCLUSION: Findings suggest that GLP-1 RAs are associated with reduced risk of MACE, and MI among people with OW/OB, but they were driven by studies with established CVD at baseline.