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Role of sulfonylureas in non-insulin-dependent diabetes mellitus: Part II--"The cons".

Non-insulin dependent diabetes mellitus carries a markedly elevated risk of cardiovascular disease. For that reason the efficacy of any treatment modality for this disease should be assessed in terms of the known cardiovascular risk factors, as for example serum lipids. Sulfonylurea do not affect serum lipid levels to any significant extent. These drugs promote beta-cell secretion by dosing potassium ion channels. These channels are also present in vascular smooth muscle cells. Some, though not all, sulfonylureas are able to inhibit the vascular dilatory response to potassium ion openers, thereby adversely affecting the cardioprotective vascular response to ischaemia. Sulfonylureas, in contrast to insulin, seem able to inhibit the fibrinolytic system, possibly via the stimulating effect of proinsulin on the endothelial PAI-1 expression. These observations need further confirmation. Of clinical importance is the frequent occurrence of hypoglycaemia for which several risk factors are recognized.