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

Bain, Steve; Druyts, Eric; Balijepalli, Chakrapani; Baxter, Carl A.; Currie, Craig J.; Das, Romita; Donnelly, Richard; Khunti, Kamlesh; Langerman, Haya; Leigh, Paul; Siliman, Gaye; Thorlund, Kristian; Toor, Kabirraaj; Vora, Jiten; Mills, Edward J.

Abstract

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.

Citation

Bain, S., Druyts, E., Balijepalli, C., Baxter, C. A., Currie, C. J., Das, R., Donnelly, R., Khunti, K., Langerman, H., Leigh, P., Siliman, G., Thorlund, K., Toor, K., Vora, J., & Mills, E. J. (2017). Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: a Bayesian meta-analysis of survival data. Diabetes, Obesity and Metabolism, 19(3), 329-335. https://doi.org/10.1111/dom.12821

• Journal Article Type: Article
• Acceptance Date: Nov 2, 2016
• Online Publication Date: Dec 23, 2016
• Publication Date: Feb 27, 2017
• Deposit Date: Jun 30, 2017
• Publicly Available Date: Jun 30, 2017
• Journal: Diabetes, Obesity and Metabolism
• Print ISSN: 1462-8902
• Electronic ISSN: 1463-1326
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 3
• Pages: 329-335
• DOI: https://doi.org/10.1111/dom.12821
• Keywords: cardiovascular disease, meta-analysis, sulphonylureas, systematic review, T2DM
• Public URL: https://nottingham-repository.worktribe.com/output/844073
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/dom.12821/abstract
• Related Public URLs: https://cronfa.swan.ac.uk/Record/cronfa31167
• Additional Information: This is the peer reviewed version of the following article: Bain, Steve and Druyts, Eric and Balijepalli, Chakrapani and Baxter, Carl A. and Currie, Craig J. and Das, Romita and Donnelly, Richard and Khunti, Kamlesh and Langerman, Haya and Leigh, Paul and Siliman, Gaye and Thorlund, Kristian and Toor, Kabirraaj and Vora, Jiten and Mills, Edward J. (2017) Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: a Bayesian meta-analysis of survival data. Diabetes, Obesity and Metabolism, 19 (3). pp. 329-335. ISSN 1462-8902 , which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/dom.12821/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.; ; The Related URL is for the version deposited in Swansea University's repository. MJB 27.03.18.
• Contract Date: Jun 30, 2017