Thiazolidinedione drugs in the treatment of type 2 diabetes mellitus: past, present and future

Crit Rev Toxicol. 2018 Jan;48(1):52-108. doi: 10.1080/10408444.2017.1351420. Epub 2017 Aug 17.


Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes. As treatment with TZDs has been associated with adverse hepatic, cardiovascular, osteological, and carcinogenic events in some studies, the role of TZDs in the treatment of T2DM continues to be debated. At the same time, new therapeutic roles for TZDs are being investigated, with new forms and isoforms currently in the pre-clinical phase for use in the prevention and treatment of some cancers, inflammatory diseases, and other conditions. The aims of this review are to provide an overview of the mechanism(s) of action of TZDs, a review of their safety for use in the treatment of T2DM, and a perspective on their current and future therapeutic roles.

Keywords: Thiazolidinedione; adverse effects; bone fracture; cancer; diabetes; drug safety; heart failure; hepatotoxicity; mechanism; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Inflammation / drug therapy
  • Male
  • Neoplasms / drug therapy
  • Neoplasms / prevention & control
  • Osteogenesis / drug effects
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / pharmacology*
  • Thiazolidinediones / therapeutic use*


  • Thiazolidinediones