Pioglitazone: side effect and safety profile

Importance of the field: Thiazolidinediones (TZDs) are useful glucose-lowering agents for patients with Type 2 diabetes. Through PPAR-gamma-mediated effects, these drugs not only improve insulin sensitivity and glycemia, they also have beneficial effects on lipid metabolism and the vascular endothelium, with potential to improve cardiovascular risk. However, this promise has not been entirely fulfilled. The first TZD, troglitazone, was withdrawn after reports of severe liver damage. The second TZD, rosiglitazone, has been reported in meta-analyses to be associated with possible increased risk of cardiovascular disease (CVD) events. The third TZD approved for clinical use in the US, pioglitazone, appears to be associated with decreased CVD events in most studies/meta-analyses. Areas covered in this review: We undertook a literature search in Pubmed from the year 2000 onwards to review the side effect/safety profile of pioglitazone. What the reader will gain: A comprehensive summary of the currently available data on the side effect/safety profile of pioglitazone. Take home message: The main adverse effects reported with pioglitazone are those common to the TZD class: weight gain, pedal edema, bone loss and precipitation of congestive heart failure in at-risk individuals, without any increase in CVD/all-cause mortality. Overall, the safety profile of pioglitazone is favorable and remains a useful option for the treatment of insulin-resistant patients with Type 2 diabetes. Further studies are needed to confirm/clarify its cardiovascular benefits.