GLP-1 Receptor Agonists and Cardiovascular Outcomes in Patients with Type 2 Diabetes Across Myocardial Infarction-Defined Populations: A Systematic Review and Meta-Analysis

Abstract

Background

Patients with type 2 diabetes mellitus (T2DM) who survive myocardial infarction (MI) remain at high risk for recurrent cardiovascular events and heart failure (HF). Although glucagon-like peptide-1 receptor agonist (GLP-1 RA) reduces cardiovascular events in stable atherosclerotic disease, its impact among patients with established MI has not been comprehensively synthesized.

Objectives

To evaluate the association between GLP-1 RA use and cardiovascular outcomes in patients with T2DM across MI-defined cohorts.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was evaluated using the I² statistic, and 95% prediction intervals (PIs) were calculated to estimate the expected range of true effects in future clinical settings. Outcomes included all-cause mortality, cardiovascular death, study-defined major adverse cardiovascular events (MACE), MI, stroke, and HF or hospitalization for HF. A sensitivity analysis using the Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment was performed to account for the small number of included studies and substantial heterogeneity. Statistical analysis was performed using R software version 4.5.0.

Results

Seven studies, including 37,393 patients with T2DM from MI-defined populations (9556 receiving GLP-1 RA), were analyzed. GLP-1 RA use was associated with lower all-cause mortality (HR, 0.67; 95% CI, 0.49–0.90; I² = 87.3%; PI, 0.27–1.63; P = 0.0085), reduced study-defined MACE (HR, 0.69; 95% CI, 0.56–0.84; I² = 55.6%; PI, 0.44–1.06; P = 0.0002), and fewer HF events or hospitalizations for HF (HR, 0.78; 95% CI, 0.62–0.98; I² = 77.6%; PI, 0.42–1.45; P = 0.0306). No significant associations were observed for cardiovascular death (HR, 0.85; 95% CI, 0.67–1.06; I² = 0%; PI, 0.42–1.69; P = 0.15), recurrent MI (HR, 0.82; 95% CI, 0.62–1.09; I² = 63%; PI, 0.41–1.63; P = 0.1753), or stroke (HR, 0.91; 95% CI, 0.68–1.22; I² = 61.2%; PI, 0.40–2.05; P = 0.5237). In the sensitivity analysis using the HKSJ adjustment, statistical significance was lost for all endpoints, including all-cause mortality (P = 0.05), study-defined MACE (P = 0.13), and HF or hospitalization for HF (P = 0.06).

Conclusions

In patients with T2DM across MI-defined populations, GLP-1 RA use showed signals toward lower all-cause mortality, study-defined MACE, and HF-related events; however, these findings remain exploratory because of substantial heterogeneity, wide PIs, and attenuation of statistical significance under HKSJ adjustment.

Registration

PROSPERO identifier no. CRD420251270326.

Graphical Abstract