Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP1RAs) are relatively newer anti-hyperglycemic agents, which have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus. Design We performed a meta-analysis of randomized controlled trials to evaluate the cardiovascular outcomes of GLP1RAs compared to placebo in type 2 diabetes mellitus patients. We performed an additional subgroup analysis to evaluate the role of GLP1RAs in patients with chronic kidney disease. Methods MEDLINE, Cochrane and ClinicalTrials.gov databases were searched from inception to 15 July 2019. The authors extracted relevant information from articles and independently assessed the study quality. Results Compared to placebo, GLP1RAs demonstrated a significant reduction in all-cause mortality (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.82–0.95; P < 0.001), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.96; P = 0.004), primary composite endpoint (OR 0.86, 95% CI 0.80–0.91; P < 0.001) and non-fatal stroke (OR 0.86, 95% 0.77–0.95; P = 0.004). There was no statistical difference in non-fatal myocardial infarction (OR 0.92, 95% CI 0.83–1.01; P = 0.09). In subgroup analyses of patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m2 and less than 30 ml/min/1.73 m2, there was no significant difference in the primary composite endpoint. Conclusions GLP1RAs demonstrated a significant reduction in all-cause mortality, cardiovascular mortality, primary composite endpoint and non-fatal stroke in patients with type 2 diabetes mellitus. There was no significant difference in the primary composite endpoint in patients with type 2 diabetes mellitus and chronic kidney disease.