Continuous versus intermittent sulphonylurea therapy in non-insulin-dependent diabetes mellitus

Although it is 50 years since the discovery of the hypoglycaemic effects of sulphonylureas, the molecular basis of their effects are still not fully understood. It has been suggested that long term sulphonylurea therapy may desensitise the pancreatic beta-cells to further drug effects, and that intermittent sulphonylurea therapy may be the best approach to maintain their effectiveness. A randomised, double-blind study has been carried out to attempt to answer the question of whether intermittent sulphonylurea therapy is more effective then continuous administration. Responders to oral glibenclamide (glyburide) went on to receive continuous or intermittent treatment (glibenclamide for 2 weeks then placebo for 2 weeks) for 16 weeks. Glycaemic control was maintained in the continuous treatment group. However, glucose levels deteriorated in the intermittent treatment group, suggesting that there is no merit to intermittent sulphonylurea treatment. Other strategies to investigate include administration on an alternate-day basis or a shorter period off the drug (e.g. 1 week). The underlying question of optimal glycaemic control with sulphonylureas warrants a definitive answer.