The Use of Sulphonylureas in the Elderly

Type 2 diabetes mellitus is a heterogeneous disorder characterised by defects in insulin secretion as well as reduced insulin action. During aging, glucose intolerance will gradually develop, and this is manifested primarily by an increase in the postprandial blood glucose response while fasting blood glucose levels are often less elevated. Abnormal beta-cell secretion of insulin is a main feature of this. Treatment of elderly patients with type 2 diabetes mellitus focuses on reduction of (hyperglycaemic) complaints and prevention of the development or progression of secondary complications. Although regular physical activity and dietary measures, aiming at bodyweight normalisation, are the cornerstones of therapy, pharmacological treatment with oral blood glucose lowering-agents often proves necessary to control the hyperglycaemia. In the United Kingdom Prospective Diabetes Study (UKPDS) it was clearly shown that patients with type 2 diabetes mellitus who were intensively treated with oral blood glucose-lowering agents or insulin developed less microvascular complications. The question whether achievement of strict metabolic control is also of benefit in elderly patients, is still unanswered. Sulphonylureas are drugs which stimulate insulin secretion by enhancing the release of insulin from the pancreatic beta-cells without an effect on insulin synthesis. They are frequently used in the treatment of type 2 diabetes mellitus, and several preparations are available. In general, there are no major differences in effectiveness between the various sulphonylureas. Long term treatment with sulphonylureas will decrease fasting and postprandial plasma glucose levels by 3 to 5 mmol/L, and glycosylated haemoglobin by 20%. However, after its initial decline, plasma glucose level will often go up slightly during the following months to years. Sulphonylureas are usually well tolerated. Hypoglycaemia is the most frequently occurring adverse effect, which may be very serious and damaging in the elderly. It has been associated primarily with long-acting sulphonylureas, like chlorpropamide and glibenclamide (glyburide). Hypoglycaemic episodes may trigger serious events like myocardial infarction or stroke. Therefore, shorter-acting compounds like tolbutamide and gliclazide have been relatively well tolerated and appear to be the best choice to treat elderly patients. It is advisable to start with a low dose and increase the dose, when needed, in small steps. The efficacy of sulphonylureas is much greater when they are taken before a meal. Because of the fact that type 2 diabetes mellitus is a progressive disease, and residual beta-cell function decreases with time, insulin therapy may ultimately be warranted in a significant number of patients.