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

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.