Update in Cardiovascular Safety of Glucagon Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes. A Mixed Treatment Comparison Meta-Analysis of Randomised Controlled Trials

Background The aim of this mixed treatment comparison (MTC) meta-analysis was to determine glucagon like peptide-1 (GLP-1) receptor agonists’ effects on cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM). Methods A comprehensive, systematic review was conducted using EMBASE and Medline databases. All included trials were large CV outcome trials of GLP-1 agonists versus placebo in T2DM. The primary outcomes of this MTC meta-analysis were death from CV causes, non-fatal MI, and non-fatal stroke. Hospitalisation for heart failure (HF) was evaluated as a secondary endpoint. Results A total of four trials, including 33,457 patients, met eligibility criteria and were retained for the meta-analysis. Our pairwise meta-analysis results showed a 13% reduction in death from cardiovascular causes in patients who received GLP-1 agonists versus placebo (RR 0.87, 95% CI: 0.78–0.96). However, no statistically significant reduction was observed with GLP-1 agonists in terms of reducing non-fatal MI (RR 0.95, 95% CI: 0.86–1.04), non-fatal stroke events (RR 0.89, 95% CI: 0.76–1.03), and rates of HF hospitalisation (RR 0.94, 95% CI: 0.84–1.04). The network meta-analysis (NMA) showed no significant differences among all the interventions. Conclusion Glucagon like peptide-1 therapy was associated with a significant reduction in cardiovascular (CV) death. However, GLP-1 agonists seem to have a safety profile comparable to placebo in terms of reducing non-fatal myocardial infarction (MI), non-fatal stroke events, and rates of HF hospitalisation.