Update in the treatment of type 2 diabetes mellitus. Insulin secreting agents.

The functional defect of the pancreatic beta cell represents one of the mai n therapeutic targets in type 2 diabetes mellitus. Among the currently avai lable oral antidiabetic drugs, only hypoglycaemic sulfonylureas exhibit bet a cell stimulating properties. However, their use has some limits, particul arly those related to the risk of hypoglycaemia and the frequent secondary therapeutic failure. These drugs have largely contributed to the knowledge of the mechanisms of insulinsecretion. Besides so,ne galenic modifications of existing sulfonylureas and the development of new drugs of this family w ith original properties, like glimepiride, the research is essentially focu sed on drugs derived from the non sulfonylurea moiety of some sulfonylureas , particularly the meglitinide family, which will probably be available for the clinician in the near future These drugs act however grossly by the sa me mechanism than sulfonylureas, even if their binding site on a protein co upled with the ATP sensitive K channel appears different. Among the other p ossible approaches suggested by the theoretical data concerning the mechani sms of insulin secretion, GLP-1 derivatives probably represent good candida tes, if stable analogues are developed. (C) 1999 Elsevier, Paris.