The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.
Type 2 diabetes results from the abnormal resistance of peripheral tissues to insulin and from the progressive insulin secretory failure of the pancreatic beta-cells. Treatment of type 2 diabetes has greatly improved due to the availability of new classes of oral antidiabetic drugs (OADs) and new insulin analogs. Three types of oral medications exert their antidiabetic action without directly stimulating insulin release: alpha-glucosidase inhibitors (e.g., acarbose) interfere with the digestion of dietary glucose precursors and the absorption of glucose; biguanides (e.g., metformin) inhibit hepatic gluconeogenesis, thereby lowering fasting blood glucose concentrations and increasing peripheral insulin sensitivity; and thiazolidinediones (e.g., rosiglitazone) improve the sensitivity of tissues to insulin-stimulated glucose disposal. In contrast, two classes of OADs stimulate insulin release from pancreatic beta-cells. Sulfonylureas (e.g., glyburide) have been used successfully for many years to treat type 2 diabetes, but their prolonged action may result in hypoglycemia. The third-generation sulfonylurea glimepiride is associated with a reduced risk of hypoglycemia and less weight gain than other sulfonylureas. Finally, the meglitinides (e.g., repaglinide) and D-phenylalanine derivatives (e.g., nateglinide) are powerful prandial insulin secretagogues. If the pancreatic beta-cells deteriorate to such an extent that insulin secretion is significantly impaired, treatment with additional exogenous insulin may be required.
Rosak
Christoph
C
Department of Diabetology and Metabolic Disorders, C.V. Noorden Klinik, Krankenhaus Sachsenhausen, Frankfurt am Main, Germany.
D000284:Administration, Oral; D001645:Biguanides / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use
D001645:Biguanides; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D013844:Thiazoles