Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: A Bayesian meta-analysis of survival data

Aim: To conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). Materials and methods: A systematic review of Medline, Embase, Cochrane and clinicaltrials. gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions. For the analysis of observational data, conventional fixed-effect pairwise meta-analyses were used. Results: The systematic review identified 82 randomized controlled trials (RCTs) and 26 observational studies. Meta-analyses of RCT data showed an increased risk of all-cause mortality and cardiovascular-related mortality for SUs compared with all other treatments combined (HR 1.26, 95% confidence interval [CI] 1.10-1.44 and HR 1.46, 95% CI 1.21-1.77, respectively). The risk of myocardial infarction was significantly higher for SUs compared with dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter-2 inhibitors (HR 2.54, 95% CI 1.14-6.57 and HR 41.80, 95% CI 1.64-360.4, respectively). The risk of stroke was significantly higher for SUs than for DPP-4 inhibitors, glucagon-like peptide-1 agonists, thiazolidinediones and insulin. Conclusions: The present meta-analysis showed an association between SU therapy and a higher risk of major cardiovascular disease-related events compared with other glucose lowering drugs. Results of ongoing RCTs, which should be available in 2018, will provide definitive results on the risk of cardiovascular events and all-cause mortality associated with SUs vs other antihyperglycaemic drugs.