Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis

Aims: Sulphonylurea use has been linked with increased cardiovascular disease risk; however, previous studies have been inconsistent. Type 2 diabetes independently increases risk for cardiovascular disease, so understanding the link between longer-term use of anti-diabetic medications and cardiovascular disease has important clinical implications.

Methods: Literature search in MEDLINE and CENTRAL was conducted throughout December 2011 for clinical and observational studies that reported the association between sulphonylurea and cardiovascular disease events. Ratios (relative risk, odds ratios or hazard ratios) adjusted for potential confounders (concomitant medications, baseline cardiovascular risk, diabetes severity) were pooled using a random-effects model to yield relative risks and associated 95% confidence intervals.

Results: This meta-analysis included 33 studies (n = 1,325,446 patients), followed for a range of 0.46-10.4 years. In all studies, compared with other oral diabetes drugs, sulphonylurea use was associated with a significantly increased risk of cardiovascular death (relative risk 1.27, 95% confidence interval 1.18-1.34, n = 27 comparisons) and composite cardiovascular event (including myocardial infarction, stroke, cardiovascular-related hospitalization or cardiovascular death) (relative risk 1.10, 95% confidence interval 1.04-1.16, n = 43 comparisons). In studies comparing sulphonylurea vs. metformin, these relative risks were 1.26 (95% confidence interval 1.17-1.35, n = 17 comparisons) and 1.18 (95%confidence interval 1.13-1.24, n = 16 comparisons), respectively.

Conclusions: Results suggest that sulphonylurea use may elevate the risk of cardiovascular disease among patients with diabetes. This meta-analysis expands the pool of studies evaluating cardiovascular mortality compared with prior observations while using adjusted estimates, and assessing an additional outcome of a composite cardiovascular event. This finding warrants consideration in clinical practice when other treatment options may be available.