Insulin-sensitising agents

Current treatments for non-insulin-dependent diabetes mellitus (NIDDM; Type 2 diabetes) remain far from ideal. The presence of both hyperinsulinaemia and resistance to insulin action challenges the rationale of treatments that primarily boost insulin secretion. Novel therapeutic strategies focus mainly on increasing peripheral sensitivity to endogenous insulin, an approach that has the potential not only to treat but also to prevent Type 2 diabetes in high-risk individuals. Until recently, the most promising new class of agents appeared to be the thiazolidinedione derivatives. These agents are ligands for a specific subtype of peroxisome proliferator activated receptor (PPAR) and decrease plasma glucose levels while reducing circulating insulin and free fatty acid levels. At the time of writing (March 1998), the one approved thiazolidinedione had been withdrawn from the market in the UK after only nine weeks because of cases of hepatic dysfunction and failure occurring in patients in Japan and the USA. It is not yet clear whether this is a class effect and hence whether it will affect other similar agents in development. Reference is made to the current status of other agents in development.