These oral agents reduce the excessive amounts of GLUCOSE in the blood (HYPERGLYCAEMIA) in people with type 2 (INSULIN-resistant) diabetes (see DIABETES MELLITUS). Although the various drugs act differently, most depend on a supply of endogenous (secreted by the PANCREAS) insulin. Thus they are of no value in treating patients with type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]), in which the pancreas produces little or no insulin and the patient's condition is stabilised using insulin injections. The traditional oral hypoglycaemic drugs have been the sulphonylureas and biguanides, but new agents are now available – for example, thiazolidine-diones (insulin-enhancing agents) and alpha-glucosidase inhibitors, which delay the digestion of CARBOHYDRATE and the absorption of glucose. Hypoglycaemic agents should not be prescribed until diabetic patients have been shown not to respond adequately to at least three months’ restriction of carbohydrate intake.
The main group of hypoglycaemic agents, these act on the beta cells to stimulate insulin release; consequently they are effective only when there is some residual pancreatic beta-cell activity (see INSULIN). They also act on peripheral tissues to increase sensitivity, although this is less important. All sulphonylureas may lead to HYPOGLYCAEMIA four hours or more after food, but this is relatively uncommon, and usually an indication of overdose.
There are several different sulphonylureas; apart from some differences in their duration or action (and hence in their suitability for individual patients) there is little difference in their effectiveness. Only chlorpropamide has appreciably more side-effects – mainly because of its prolonged duration of action and consequent risk of hypoglycaemia. There is also the common and unpleasant chlorpropamide/alcohol-flush phenomenon when the patient takes alcohol. Selection of an individual sulphonylurea depends on the patient's age and renal function, and often just on personal preference. Elderly patients are particularly prone to the risks of hypoglycaemia when long-acting drugs are used. In these patients, doctors often advise avoiding chlorpropamide, and glibenclamide, in favour of gliclazide or tolbutamide.
These drugs may cause weight gain and are indicated only if poor control persists despite adequate attempts at dieting. They should not be used during breast feeding, and caution is necessary in the elderly and in those with renal or hepatic insufficiency. They should also be avoided in porphyria (see PORPHYRIAS). During surgery and intercurrent illness (such as MYOCARDIAL INFARCTION, COMA, infection and trauma), insulin therapy should be temporarily substituted. Insulin is generally used during pregnancy and should be used in the presence of ketoacidosis.
Chiefly gastrointestinal disturbances and headache; these are generally mild and infrequent. After drinking alcohol, chlorpropamide may cause facial flushing. It also may enhance the action of antidiuretic hormone (see VASOPRESSIN), very rarely causing HYPONATRAEMIA.
Sensitivity reactions are very rare, usually occurring in the first six to eight weeks of therapy. They include transient rashes, which rarely progress to erythema multiforme (see under ERYTHEMA), and exfoliate DERMATITIS, fever and jaundice; chlorpropamide may also occasionally result in photosensitivity. Rare blood disorders include THROMBOCYTOPENIA, AGRANULOCYTOSIS and aplastic ANAEMIA.
Metformin, the only available member of this group, acts by reducing GLUCONEOGENESIS and by increasing peripheral utilisation of glucose. It can act only if there is some residual insulin activity, hence it is only of value in the treatment of non-insulin dependent (type 2) diabetics. It may be used alone or with a sulphonylurea, and is indicated when strict dieting and sulphonylurea treatment have failed to control the diabetes. It is particularly valuable in overweight patients, in whom it may be used first. Metformin has several advantages: hypoglycaemia is not usually a problem; weight gain is uncommon; and plasma insulin levels are lowered. Gastrointestinal side-effects are initially common, and may be persistent in some patients, especially when high doses are being taken. Lactic acidosis is a rarely seen hazard occurring in patients with renal impairment, in whom metformin should not be used.
Acarbose is an inhibitor of intestinal alpha glucosidases (enzymes that process GLUCOSIDES), thus delaying the digestion of starch and sucrose, and slowing the increase in blood glucose concentrations that normally occurs after a meal containing carbohydrate. It has been introduced for the treatment of type 2 patients inadequately controlled by diet or diet with oral hypoglycaemics.
Guar gum, if taken in adequate doses, acts by delaying carbohydrate absorption, therefore reducing the postprandial blood glucose levels. It is also used to relieve symptoms of the DUMPING SYNDROME.