Cardiovascular safety and glycemic control of glucagon-like peptide-1 receptor agonists for type 2 diabetes mellitus: A pairwise and network meta-analysis

AIMS: Integrating evidence from all randomized controlled trials (RCTs) of glucagon-like peptide-1 receptor agonists (GLP-1s) to assess the safety of cardiovascular disease (CVD) and efficacy of glycemic control. METHODS: Besides performing pairwise meta-analysis, network meta-analysis of all RCTs was used to combine direct and indirect estimates of the effect of GLP-1 with placebo, active comparator drugs (ACD), or another GLP-1 agent with treatment duration ≥8 weeks in T2DM patients, 15,883 for CVD safety from 45 RCTs and 14,136 for glycemic control from 36 RCTs. RESULTS: For CVD safety, both of the results from pairwise and network meta-analysis failed to demonstrate significant difference between any two comparators. For glycemic control, the effect of any GLP-1 was better than placebo, but no difference was found between GLP-1s. We also found that liraglutide was the only GLP-1 drug shown to be more effective on improving glycemic control than ACD and exenatide. The results based on direct or indirect estimates were similar for two outcomes. CONCLUSION: Our network meta-analysis provides a complete picture of the associations between GLP-1s, ACD and placebo on CVD safety and glycemic control. The GLP-1s are promising candidates for the treatment of T2DM, but more long-term trials are needed to confirm potential CVD safety.