How safe is the use of thiazolidinediones in clinical practice?

Expert Opin Drug Saf. 2009 Jan;8(1):15-32. doi: 10.1517/14740330802597821.


Background: Thiazolidinediones (TZDs) are widely used antidiabetic drugs with proven efficacy regarding mainly surrogate markers of diabetes management. However, efficacy on surrogate markers may not always translate into benefits in clinical outcomes. Thiazolidinediones are usually well tolerated; however, their use may be associated with several adverse effects. The first TZD, troglitazone, was withdrawn from the market owing to serious hepatotoxicity. However, this does not seem to be the case with newer TZDs.

Objective: The aim of the present review is to discuss the safety profile of this drug class.

Methods: We searched PubMed up to July 2008 using relevant keywords.

Conclusions: Common side effects associated with TZDs include edema, weight gain, macular edema and heart failure. Moreover, they may cause hypoglycemia when combined with other antidiabetic drugs as well as decrease hematocrit and hemoglobin levels. Increased bone fracture risk is another TZD-related side effect. Thiazolidinediones tend to increase serum low density lipoprotein cholesterol levels, with rosiglitazone having a more pronounced effect compared with pioglitazone. Moreover, rosiglitazone increases low density lipoprotein particle concentration in contrast to pioglitazone where a decrease is observed. Rosiglitazone has been associated with an increase in myocardial infarction incidence. On the other hand, pioglitazone may reduce cardiovascular events. Overall, TZDs are valuable drugs for diabetes management but physicians should keep in mind that they are associated with several adverse events, the most prominent of which is heart failure.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Interactions
  • Fractures, Bone / chemically induced
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Macular Edema / chemically induced
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use
  • Weight Gain


  • Hypoglycemic Agents
  • Thiazolidinediones