Netoglitazone -: Antidiabetic -: PPARα/PPARγ agonist

Diabetes mellitus is a worldwide health problem that affects more and more people every year. Several drugs are available for the treatment of diabetes mellitus including various insulin formulations, biguanides, sulfonylureas, alpha-glucosidase inhibitors, insulin secret-agogues and insulin sensitizers. However, the search for more effective agents is ongoing. The insulin sensitizers or enhancers of insulin action improve insulin resistance in type 2 diabetes by increasing the sensitivity of cells to insulin and one novel class are the peroxisome proliferator-activated receptor (PPAR) agonists such as the thiazolidinediones or so-called glitazones. Thiazolidinediones (e.g., troglitazone, rosiglitazone, pioglitazone), the first high-affinity PPARgamma agonists discovered, do not increase insulin secretion or the number or affinity of insulin receptor binding sites but are thought to amplify postreceptor events in the insulin signaling cascade. Of these compounds, netoglitazone (MCC-555) which possesses both PPARalpha and PPARgamma agonist activity has displayed potent preclincial activity and was selected for further clinical development as a treatment of diabetes. This article discusses the synthesis and the extensive pharmacological actions of this new agent.