Oral hypoglycaemic agents. An update.

Despite the availability of oral hypoglycaemic agents for nearly 30 years, their precise mode of action and role in the management of diabetes mellitus remains poorly defined and controversial. They are regarded by many, though not all, clinicians as helpful adjuncts in the treatment of patients with non-insulin-dependent diabetes who have failed to respond satisfactorily to an adequate programme of dietary treatment. Their initial effectiveness is greatest in those patients who have had diabetes for less than 5 years, are overweight at the time of initiation of therapy, and whose fasting blood glucose levels are not unduly raised (less than 200 mg/dl). If they are receiving treatment with insulin and a shift to oral compounds is contemplated, success in the changeover is more likely if the daily dose has been less than 20 to 30 units daily. While their efficacy in maintaining adequate glycaemic control over the short term in responsive patients is unquestioned, the long term benefit of oral hypoglycaemic agents in reducing morbidity and mortality of late complications remains to be substantiated. In this regard, where long term efficacy is difficult to quantify, physician vigilance for chronic toxicity assumes a special importance. Notwithstanding the potential for interaction between sulphonylureas and numerous other drugs, significant adverse effects are uncommon. Hypoglycaemia is the major health concern associated with the use of sulphonylureas, and lactic acidosis has been the major problem with biguanides. Careful patient selection is thus the key to ensuring efficacy and avoiding toxicity. Recent evidence suggests that while the insulinotropic action of the sulphonylureas may explain the short term hypoglycaemic effect of these compounds, their reported action in enhancing insulin sensitivity, both at the receptor and post-receptor levels, more likely accounts for the long term maintenance of improved carbohydrate tolerance. The relatively new ('second generation') sulphonylurea compounds have not been shown to possess clearly defined advantages over the older preparations; the potentially beneficial effects of gliclazide on the microangiopathic changes of diabetes require considerable further evaluation.