Association of sulphonylurea treatment with all-cause and cardiovascular mortality: A systematic review and meta-analysis of observational studies

We conducted a meta-analysis of cohort and case-control studies to evaluate all-cause and cardiovascular (CV) mortality of patients with type 2 diabetes mellitus (T2DM) who received sulphonylurea (SU) treatment, when compared to any other diabetes treatment. Only studies reporting raw data on mortality during SU treatment were included. Data were combined using random-effects (RE) models. Unadjusted odds ratios (ORs) are presented. Of 4991 publication titles and abstracts reviewed, 20 studies (n = 551,912 patients) were included. For cohort studies (n = 276,050), patients receiving SU monotherapy or combination treatment had significantly higher all-cause and CV mortality risks compared to any non-SU treatment [all-cause, 13 studies: OR = 1.92, 95% confidence interval (CI) = 1.48-2.49; CV, 5 studies: OR = 2.72, 95% CI = 1.95-3.79]. Validity was limited by the high treatment group heterogeneity (I-2 > 90%) and study-inherent biases/design differences. In conclusion, patients receiving SU treatment had increased all-cause and CV mortality risks. However, the meta-analysis was limited by the high heterogeneity of non-randomized studies.