GLP-1 receptor agonists reduce infarct size relative to area at risk in myocardial infarction: a meta-analysis of randomized controlled trials

Background

GLP-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events in patients with diabetes, but their impact on myocardial injury in acute myocardial infarction (MI) remains unclear.

Purpose

To our knowledge, no meta-analysis has evaluated the effect of GLP-1 RAs on infarct size. We performed a meta-analysis of randomized controlled trials to quantify their effect on infarct size relative to the area at risk (AAR).

Methods

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Major databases (MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and Google Scholar) were searched from inception through February 2026 for comparative studies evaluating the effect of GLP-1 RAs on infarct size. The goal was to identify studies comparing GLP-1 RAs (exenatide or liraglutide) versus placebo in patients with acute MI reporting infarct size.

The primary outcome was infarct size as a percentage of AAR. Mean differences (MD) were pooled using random-effects meta-analysis (REML, Hartung-Knapp adjustment), with fixed-effect analysis performed as a sensitivity analysis. Heterogeneity was quantified using I². Forest plots were generated for visualization. Three RCTs were included (Lønborg et al., 2012; Bernink et al., 2013; Chen et al., 2016), totaling 205 patients. All studies focused on patients with ST-segment-elevation myocardial infarction (STEMI). Analysis was conducted using R version 4.5.2 software.

Results

Across the three RCTs, GLP-1 RAs significantly reduced final infarct size relative to the area at risk compared with placebo. The random-effects pooled mean difference was –10.14% (95% CI: –14.11% to –6.17%, p < 0.001) (Figure 1). All studies favored GLP-1 therapy. Fixed-effect sensitivity analysis yielded similar results.

Conclusions

GLP-1 receptor agonists significantly reduce infarct size relative to AAR in acute MI, supporting a potential cardioprotective effect beyond glycemic control. These findings suggest that GLP-1 RAs may attenuate myocardial injury in MI, particularly in STEMI patients. Large-scale randomized trials are warranted to confirm these cardioprotective benefits and to assess clinical outcomes.Figure 1:Effect of GLP-1 RAs