Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus?

Thiazolidinediones have been introduced in the treatment of type 2 diabetes mellitus (T2DM) since the late 1990s. Although troglitazone was withdrawn from the market a few years later due to liver toxicity, both rosiglitazone and pioglitazone gained widespread use for T2DM treatment. In 2010, however, due to increased risk of cardiovascular events associated with its use, the European Medicines Agency recommended suspension of rosiglitazone use and the Food and Drug Administration severely restricted its use. Thus pioglitazone is the only thiazolidinedione still significantly employed for treating T2DM and it is the only molecule of this class still listed in the American Diabetes Association-European Association for the Study of Diabetes 2012 Position Statement. However, as for the other thiazolidinediones, use of pioglitazone is itself limited by several side effects, some of them potentially dangerous. This, together with the development of novel therapeutic strategies approved in the last couple of years, has made it questionable whether or not thiazolidinediones (namely pioglitazone) should still be used in the treatment of T2DM. This article will attempt to formulate an answer to this question by critically reviewing the available data on the numerous advantages and the potentially worrying shortcomings of pioglitazone treatment in T2DM.