ANTIDIABETIC AGENTS have a number of mechanisms of action. The most frequently used drugs are essentially antihyperglycaemic agents; often called hypoglycaemics. These are used principally in the treatment of diabetes mellitus. Such drugs are quite distinct from those used to treat diabetes insipidus (see ANTIDIURETIC AGENTS). There are several types of antidiabetic treatment for diabetes mellitus.
Firstly, insulin, which is used mainly in Type 1 diabetes (insulin-dependent diabetes mellitus; IDDM; juvenile-onset diabetes) cannot be taken by mouth and must be injected. Insulin is a protein hormone produced and secreted by the β-cells of the Islets of Langerhans within the pancreas. It has the effect of reducing the level of glucose in the blood, and is part of a balancing mechanism with the opposing hormone glucagon, which increases blood glucose. Its deficiency disorder — diabetes mellitus — therefore can result in hyperglycaemia, which can rapidly lead to severe symptoms, and potentially coma and death. There are many insulin preparations available, of both human and animal sequences, differing mainly in their duration of action.
Secondly, oral hypoglycaemics are synthetic agents taken by mouth to reduce the levels of blood glucose, and are used mainly in the treatment of Type 2 diabetes (non-insulin-dependent diabetes mellitus; NIDDM; maturity-onset diabetes) when there is still some residual capacity in the pancreas for the production of insulin (but often with insulin-resistance developing at insulin receptors). The major types are sulphonylureas (e.g. chlorpropamide, glibenclamide, glipizide and tolbutamide) and biguanide drugs (e.g. metformin). The major mechanism of action of the sulphonylureas is to increase insulin secretion from the β-cells by acting on certain ATP-sensitive K+-channels (see POTASSIUM-CHANNEL BLOCKERS).
Acarbose inhibits the enzymatic conversion in the intestine of starch and sucrose to glucose (it is an α-glucosidase inhibitor). It has recently been introduced for the treatment of Type 2 diabetes. Lastly, there are a number of other directions being considered in diabetic diagnosis and treatment, including analogues of amylin (islet amyloid polypeptide): see AMYLIN RECEPTOR AGONISTS. There are a number of new oral hypoglycaemic drugs under development, such as the thiazolidinediones (e.g. the thiazole troglitazone), which enhance the response of tissues to insulin. New types of drug action may be used to treat diabetes; inhibitors of fatty acid oxidation; β3-adrenoceptor agonists may be useful (see β-ADRENOCEPTOR AGONISTS); and reintroduction of vanadium salts is now being advocated (as vanadyl sulphate, sodium orthovanadate and sodium metavanadate) and clinical trial successes are reported.