ALPHA-GLUCOSIDASE INHIBITORS AS AGENTS IN THE TREATMENT OF DIABETES

Although the gastrointestinal tract does not play a significant role i n the pathogenesis of either type 1 or type 2 diabetes, modification o f its physiological activities can be used to improve glycemic and lip id control in these disorders. alpha-Glucosidase inhibitors are drugs that delay digestion of complex carbohydrates by acting as competitive inhibitors of the intestinal alpha-glucosidase enzymes that hydrolyze oligosaccharides into monosaccharides. This decreases rises in postpr andial plasma glucose. As a consequence of their pharmacological actio n, alpha-glucosidase inhibitors also cause a concomitant decrease in p ostprandial plasma insulin and gastric inhibitory polypeptide and a ri se in late postprandial plasma glucagon-like peptide 1 levels. In indi viduals with normal or impaired glucose tolerance with hyperinsulinemi a, alpha-glucosidase inhibitors decrease hyperinsulinemia and improve insulin sensitivity. In patients with type 2 diabetes, alpha-glucosida se inhibitors when added to a high-carbohydrate diet treatment lower f asting plasma glucose by a mean of 24 mg/dl, postprandial plasma gluco se by a mean of 54 mg/dl, and HbA(1c) by a mean of 0.90%. When added t o the treatment of type 2 diabetic patients on insulin, metformin, or sulfonylureas, there is an additional decrease in HbA(1c) of 0.54, 0.7 3, and 0.85%, respectively. In type 1 diabetic patients, alpha-glucosi dase inhibitors can be used to reduce postprandial glycemic excursions and decrease postprandial hypoglycemia. Additional benefits of alpha- glucosidase inhibitors in the treatment of patients with type 2 diabet es are a lack of hypoglycemia with monotherapy, an excellent safety pr ofile, and a modest decrease in postprandial plasma triglyceride level s. The major adverse events associated with a glucosidase inhibitor tr eatment are flatulence, abdominal discomfort, and bloating. These effe cts are the consequences of undigested carbohydrate reaching the colon , where it is fermented by the bacteria. Appropriate dosing-which incl udes starting with a very low dose of the drug, titrating the dose upw ards very slowly, and not increasing the dose beyond that which maxima lly benefits glycemic control-will significantly decrease these gastro intestinal side effects. The alpha-glucosidase inhibitors available in the U.S. are acarbose and miglitol.