Association of glucagon-like peptide-1 receptor agonist use and rates of acute myocardial infarction, stroke and overall mortality in patients with type 2 diabetes mellitus in a large integrated health system

Aims: To assess the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. Research Design and Methods: Patients who had T2D between 2005 and 2014 (N = 105 862) were identified from the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes. The findings were further evaluated by assessing the effect of GLP-1RAs on the same variables in patients with and without prior CVD. The model adjusted for differences in demographic information, hypertension, laboratory/vital signs, history of outcomes, and T2D medications. Results: There were significantly lower rates of AMI (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65 to 0.99; P =.045), CVA (HR 0.82, 95% CI 0.74 to 0.91, P <.001), overall mortality (HR 0.48, 95% CI 0.41 to 0.57; P <.001), and the composite outcome (HR 0.82, 95% CI 0.74 to 0.91; P <.002) during the consolidated time that patients were exposed to GLP-1RAs compared to corresponding rates during intervals without GLP-1RA exposure. GLP-1RA treatment was associated with a significant decrease in CVA, mortality, and the composite outcome in patients with and without established CVD, not significantly affecting AMI in these subgroups. Conclusions: GLP-1RA exposure was found to be associated with a reduction in the risk of cardiovascular events observed and overall mortality among patients with T2D with and without established CVD, after adjusting for potential confounders.