The safety of thiazolidinediones

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) has reached epidemic proportions. Many new therapies have emerged, including thiazolidinediones (TZDs), selective agonists of PPAR-γ, now used as both primary and add-on therapies. Given that T2DM is a lifetime disease, there is a need for assurance that new drugs are both safe and effective. Recent concern about the cardiovascular safety of one of the new drugs, rosiglitazone, is the stimulus for this review. Areas covered: The safety of pioglitazone and rosiglitazone under the headings of liver safety, cardiovascular safety, fluid retention, weight gain and bone fractures is reviewed based on a PubMed search of the years 1997 through June 2010. This review also describes the magnitude of the risks of the TZDs and provides a recommendation on the use of TZDs. Expert opinion: Liver safety is no longer an issue with the TZDs. There are no significant differences between rosiglitazone and pioglitazone in fluid retention, weight gain and bone fractures. However, pioglitazone tends to be cardioprotective while rosiglitazone is cardiotoxic. There is no current justification for prescribing rosiglitazone.