Comparative tolerability of sulphonylureas in diabetes mellitus

The sulphonylurea drugs have been the mainstay of oral treatment for patien ts with diabetes mellitus since they were introduced. In general, they are well tolerated, with a low incidence of adverse effects, although there are some differences between the drugs in the incidence of hypoglycaemia. Over the years, the drugs causing the most problems with hypoglycaemia have bee n chlorpropamide and glibenclamide (glyburide), although this is a potentia l problem with all sulphonylureas because of their action on the pancreatic beta cell, stimulating insulin release. Other specific problems have been reported with chlorpropamide that occur o nly rarely, if at all, with other sulphonylureas. Hyponatraemia secondary t o inappropriate antidiuretic hormone activity, and increased flushing follo wing the ingestion of alcohol, have been well described. The progressive beta cell failure with time results in eventual loss of eff icacy, as these agents depend on a functioning beta cell and are ineffectiv e in the absence of insulin-producing capacity. Differences in this seconda ry failure rate have been reported, with chlorpropamide and gliclazide havi ng lower failure rates than glibenclamide or glipizide. The reasons for thi s are unclear, but the more abnormal pattern of insulin release produced by glibenclamide may be partly responsible and, indeed, may explain the incre ased risk of hypoglycaemia with this agent. Previously reported increased mortality associated with tolbutamide therapy has not been substantiated, and more recent data have shown no increased m ortality from sulphonylurea treatment. Indeed, benefit from glycaemic contr ol, regardless of the agent used - insulin or sulphonylurea - was reported by the United Kingdom Prospective Diabetes Study. Nevertheless, there is st ill ongoing controversy in view of the experimental evidence, mainly from a nimal studies, of potential adverse effects on the heart from sulphonylurea s, but these are difficult to extrapolate into clinical situations. Most of these studies have been carried out with glibenclamide, which makes compar ison of possible risk difficult. Other cardiovascular risk factors may be modified by gliclazide, which seem s unique among the sulphonylureas in this respect. Its reported haemobiolog ical and free radical scavenging activity probably resides in the azabicycl o-octyl ring structure in the side chain. Reduced progression or improvemen t in retinopathy has been reported in comparative trials with other sulphon ylureas, and the effect is unrelated to improvements in glycaemia. \ There are differences between the sulphonylureas in some adverse effects, r isk of hypoglycaemia, failure rates and actions on vascular risk factors. A s a group of drugs, they are very well tolerated, but differences in overal l tolerability can be identified.