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