GLP-1 Receptor Agonists and Cardiovascular Outcomes in Patients with Type 2 Diabetes Across Myocardial Infarction-Defined Populations: A Systematic Review and Meta-Analysis.
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.
To evaluate the association between GLP-1 RA use and cardiovascular outcomes in patients with T2DM across MI-defined cohorts.
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.
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).
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.
PROSPERO identifier no. CRD420251270326.
To evaluate the association between GLP-1 RA use and cardiovascular outcomes in patients with T2DM across MI-defined cohorts.
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.
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).
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.
PROSPERO identifier no. CRD420251270326.
Authors
Batista Batista, Dos Santos Silva Dos Santos Silva, Montenegro Montenegro, Malik Malik, Dandamudi Dandamudi, de Oliveira de Oliveira, Molinari Molinari, de Lucena de Lucena, Huntermann Huntermann, Giorgi Giorgi, Bacca Bacca
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