Glucagon-like peptide-1 receptor agonist in myocardial infarction and atherosclerotic cardiovascular disease risk reduction: a comprehensive meta-analysis of number needed to treat, efficacy and safety

Background: Glucagon like peptide-1 receptor agonist (GLP-1RA) use in individuals with high atherosclerotic cardiovascular disease (ASCVD) risk reduces major adverse cardiovascular events (MACE). However, its clinical impact, in terms of numbers needed to treat (NNT), efficacy and safety profile in reducing the risk of myocardial infarction (MI) and the individual ASCVD constituents remain unclear. Methods: Electronic databases, Medline and Embase were reviewed for randomized trials from inception to 29 May 2025. Risk-reduction effect of GLP-1RA were pooled using pairwise meta-analysis with random-effects model. The primary outcome was MI, and secondary outcomes were the individual ASCVD constituents. Results: 109,846 patients from 25 unique studies were included. Over a follow-up duration of 3.48 ± 1.51 (1.55 to 5.47) years, GLP-1RA reduced the risk of total MI (RR: 0.86, p < 0.01), with numbers needed to benefit (NNTB) of 207 to prevent one event of MI. Higher body mass index was associated with greater MI risk reduction (β: -0.09, p = 0.03) in GLP-1RA users. GLP-1RA reduced cardiovascular mortality (RR: 0.87, p < 0.01, NNTB 170), MACE (RR: 0.87, p < 0.01, NNTB 67) and stroke (RR: 0.88, p < 0.01, NNTB 335) compared to placebo. GLP-1RA commonly resulted in gastrointestinal side-effects amongst other systems (RR: 1.55, p < 0.01, NNTH 9). Conclusion: GLP-1RA reduced the risk of MI, stroke, cardiovascular mortality and MACE in a broad range of patients with and without T2DM and/or prior ASCVD, supporting its role in ASCVD prevention, especially in the cohort with high BMI. Trial registration: Open Science Framework (https://doi.org/10.17605/OSF.IO/7VXN5).