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

Diabetes Obes Metab. 2017 Nov;19(11):1555-1561. doi: 10.1111/dom.12969. Epub 2017 Jul 5.

Abstract

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.

Keywords: cardiovascular disease; cardiovascular risk; glucagon-like peptide-1 receptor agonist; mortality; type-2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Delivery of Health Care, Integrated
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetic Angiopathies / mortality
  • Diabetic Angiopathies / prevention & control
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mortality
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / prevention & control
  • Retrospective Studies
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / prevention & control

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents