[Increased cardiovascular risk in patients with type 2 diabetes treated with sulfonylurea?]

Abstract

Background: The use of sulphonylureas for type 2 diabetes has been debated since 1970, when the University Group Diabetes Program (UGDP) reported increased cardiovascular mortality with tolbutamide treatment.

Material and methods: We try to present a balanced review of the current knowledge of the possible cardiovascular side effects of sulphonylureas.

Results: Recent studies on the molecular actions of sulphonylureas show that sulphonylureas, in addition to closing K+ ATP channels in insulin producing cells, also do so in the myocard and in vascular smooth muscle. This action could theoretically have adverse effects during ischaemia. Experimental studies show effects on cardiac parameters and also differences in such effects between sulphonylureas, but leave the net effect of sulphonylureas during ischaemia uncertain. The United Kingdom Prospective Diabetes Study (UKPDS), published in September 1998, found no increase in cardiovascular mortality with the use of sulphonylureas. One possible explanation for the difference in relation to the UGDP is the exclusion of cardiovascular patients in the UKPDS.

Interpretation: Our interpretation is that sulphonylureas are without clinically important cardiovascular side effects in type 2 diabetic patients without cardiovascular disease. Clinical studies focusing on the effects of sulphonylurea in cardiovascular patients are, however, lacking. More studies are also needed on the effect of newly developed and possibly more selective sulphonylureas as well as related compounds.