ORAL ANTIDIABETIC AGENTS - A GUIDE TO SELECTION

Type 2 diabetes mellitus (formerly named non-insulin-dependent diabete s mellitus or NIDDM) is a heterogeneous disease resulting from a dynam ic interaction between defects in insulin secretion and insulin action . Various pharmacological approaches can be used to improve glucose ho meostasis via different modes of action: sulphonylureas essentially st imulate insulin secretion, biguanides (metformin) act by promoting glu cose utilisation and reducing hepatic glucose production, alpha-glucos idase inhibitors (acarbose) slow down carbohydrate absorption from the gut and thiazolidinediones (troglitazone) enhance cellular insulin ac tion on glucose and lipid metabolism. These pharmacological treatments may be used individually for certain types of patients, or may be com bined in a stepwise fashion to provide more ideal glycaemic control fo r most patients. Selection of oral antihyperglycaemic agents as first- line drug or combined therapy should be based on both the pharmacologi cal properties of the compounds (efficacy and safety profile) and the clinical characteristics of the patient (stage of disease, bodyweight, etc.). Mildly hyperglycaemic patients should preferably be treated wi th metformin, acarbose or thiazolidinediones (which are not associated with any hypoglycaemic risk), while more severely hyperglycaemic indi viduals should receive a sulphonylurea. In moderately hyperglycaemic p atients, sulphonylureas should be preferred in nonobese patients while metformin, and probably also thiazolidinediones, should have priority in obese insulin-resistant type 2 diabetic patients. Acarbose is main ly indicated to reduce post-prandial glucose fluctuations and improve glycaemic stability. Each antihyperglycaemic agent may also be combine d with insulin therapy to improve glycaemic control and/or reduce the insulin requirement of diabetic patients after secondary failure to or al treatment. Finally, safety should be taken into account in elderly patients and/or those with renal impairment, especially as far as the use of sulphonylureas (higher risk of hypoglycaemia) and metformin (hi gher risk of lactic acidosis) is concerned.