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  • Title: [Oral antidiabetic agents: recent aspects].
    Author: Keller U, Berger W.
    Journal: Schweiz Med Wochenschr; 1983 Apr 30; 113(17):645-50. PubMed ID: 6191388.
    Abstract:
    Sulfonylureas are the most potent and widely used oral antidiabetic agents. Despite the finding of possible side effects in a large multicenter trial (UGDP Study) demonstrating increased cardiovascular mortality during tolbutamide therapy, prescription of sulfonylureas has not declined in view of the inconclusive results of the study. In addition, new aspects of their mode of action have been discovered. Sulfonylureas may enhance insulin sensitivity of peripheral tissues, particularly by raising the decreased number of insulin receptors in type II diabetics. While this extrapancreatic effect appears to be quantitatively important, it is only present when insulin secretion is simultaneously stimulated. Insulin release is enhanced due to an increase in the sensitivity of the B-cell to glucose challenge. There is evidence to suggest that the extrapancreatic effect of sulfonylureas is secondary to their pancreatic effect. Pointers in the same direction emerged from our own results in a study on the influence of sulfonylureas added to insulin therapy on insulin sensitivity in type I diabetics. Sulfonylureas failed to increase insulin sensitivity and insulin requirements in these patients. The first generation compounds of sulfonylureas are associated with more side effects and drug interactions than the second generation preparations. However, the latter are more frequently associated with hypoglycemia since they are more potent and have a prolonged duration of action. Biguanides have almost fallen into disuse as therapeutic agents due to the potentially lethal complication of lactic acidosis. Only metformin may still be indicated in certain cases. Inhibitors of intestinal amylase and glucosidase represent a new therapeutic principle in diabetes therapy whose aim is to reduce postprandial hyperglycemia. Their value as therapeutic agents is not yet clearly established.
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