Review: Sulphonylureas and cardiovascular risk: facts and controversies

Abstract

Cardiovascular complications are the principal cause of death in type 2 diabetes. The importance of glycaemic control in preventing cardiovascular complications has been demonstrated. However, some oral antidiabetic agents and especially some sulphonylureas (SU) have been accused of having a deleterious effect on cardiovascular risk. A retrospective analysis of the administrative database of Saskatchewan Health for 5,795 subjects, identified by their first-ever dispensation for an oral antidiabetic agent, suggests that a higher exposure to SUs was associated with increased mortality. Nevertheless, the effects of SUs on cardiac ATP-sensitive potassium channels in experimental studies vary between agents and studies, so that the clinical relevance of this phenomenon is unclear. Moreover, 11 years of follow-up of patients randomised to glibenclamide or chlorpropamide in the United Kingdom Prospective Diabetes Study demonstrated no adverse effects on a range of cardiovascular end points. Despite SU structural differences and differences in binding to cardiac SU receptors, the clinical evidence base does not support the selection of one sulphonylurea over another on the basis of ischaemic preconditioning, possibly because ischaemic preconditioning may be blunted or absent in diabetes. The main objective remains the prevention or delay of diabetic complications through improvement of glycaemic control together with other cardiovascular risk factors.