[Sulphonylurea derivatives and the cardiovascular system]

Abstract

Sulphonylurea derivatives (SUD) are a mainstay of treatment of type 2 diabetes but questions have been raised about the potential adverse effects of these drugs as far as cardiovascular functions are concerned. An early prospective study which examined the effects of glycaemic control with various agents on coronary heart disease was stopped in the 70-ies due to excess cardiovascular mortality in the group receiving SUD of first generation: tolbutamide. The discovery of ATP-sensitive potassium channels in the heart, their role in ischaemic heart disease and mechanisms of endogenous cardiac cell protection--preconditioning have brought back concerns of SUD safety. Recently, a new SUD--glimepiride--claimed as the first representant of III generation of these agents--has been introduced into clinical practice. Glimepiride appears to be devoid of vascular ATP-sensitive potassium channels binding properties. Postulated and confirmed in animal experimental studies cardioprotective features of glimepiride were evaluated in a randomised, placebo-controlled study with glimepiride and glibenclamide comparing effects of these drugs on ischaemic preconditioning during angioplasty of high grade coronary artery stenoses in patients with stable angina. Myocardial ischaemia was quantified by intracoronary electrocardiography and time to occurrence of angina during vessel occlusion was measured. The results of the study confirmed glimepiride effects of maintaining myocardial preconditioning. The article summarises current knowledge of SUD influence on cardiovascular system and discusses some differences in pharmacodynamics of glimepiride which appear to provide this agent with clinical advantages over conventional SUD at least in cardiovascular aspects.