Glucagon-like peptide-1 receptor agonists and their benefits and safety in heart attack and artery disease: a detailed analysis of treatment effectiveness
GLP-1 receptor agonists reduced the risk of myocardial infarction by 14%, with a of 207 to prevent one event.
Among 109,846 patients across 25 studies, GLP-1 receptor agonists demonstrated a significant reduction in .
The risk of cardiovascular mortality was reduced by 13% with a numbers needed to treat of 170.
A 12% reduction in stroke risk was observed, with a numbers needed to treat of 335.
Higher body mass index was linked to a greater reduction in myocardial infarction risk among GLP-1 receptor agonist users.
Gastrointestinal side effects were commonly reported, with a numbers needed to harm of 9.
Simplified
BACKGROUND: Glucagon like peptide-1 receptor agonist (GLP-1RA) use in individuals with high atherosclerotic cardiovascular disease (ASCVD) risk reduces (MACE). However, its clinical impact, in terms of (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 ).
Key numbers
207
for Total MI Reduction
to prevent one event of total myocardial infarction over 3.48 years
170
for Cardiovascular Mortality Reduction
to prevent one event of cardiovascular mortality
67
for Reduction
to prevent one event of
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Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The study was exempt from IRB review as no confidential information was involved. Consent for publication: Not applicable. All other authors of the manuscript do not have a conflict of interest to declare. Authorship statement: All authors approve the final version of the manuscript, including the authorship list and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Presentations: No part of this manuscript or its contents have been presented in any capacity outside of this manuscript as of the time of submission. Registration and protocol: This review was registered on the Open Science Framework (OSF) registries prior to conduction ( https://doi.org/10.17605/OSF.IO/7VXN5 ). Competing interests: Dr Nicholas Chew is supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National University of Singapore Yong Loo Lin School of Medicine’s Academic Fellowship Scheme, and NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS).
