Metabolic effects of sulfonylurea drugs. A review

Although sulfonylureas have been used in the treatment of type 2 diabetes for more than 25 years, their mode of action is still largely unresolved. A number of pancreatic and extrapancreatic effects have been invoked to explain the hypoglycemic action of the drugs. It seems established that sulfonylureas enhance insulin secretion during short- and, possibly, also during long-term therapy, but differences between the various drugs are possible. Preserved beta-cell function is, however, a prerequisite for the blood glucose-lowering effects of these drugs. Among these, suppression of hepatic glucose production and enhancement of peripheral insulin sensitivity are clinically the most important. Reported effects relating to other hormones have proved difficult to confirm, and can often be explained by simultaneous changes in insulin secretion. Recent data provide evidence that sulfonylureas may differ in their metabolic effects. However, it remains to be determined, whether the differences are real or a consequence of different pharmacokinetics.