The current role of thiazolidinediones in diabetes management

Arch Toxicol. 2016 Aug;90(8):1861-81. doi: 10.1007/s00204-016-1737-4. Epub 2016 May 10.


Among the epidemics of modern time, type 2 diabetes mellitus (T2DM) is one of the main contributors to overall morbidity as well as mortality. A number of different treatment options are available for the management of diabetes. Among them thiazolidinediones (TZDs) is an interesting drug class since it does not target the result of T2DM, i.e., hyperglycemia but rather some of the core mechanisms of the disease. Indeed, glitazones increase insulin sensitivity by activating the peroxisome proliferator-activated receptor γ, which plays an important role in regulating various metabolic parameters. Although TZDs have an established efficacy in T2DM treatment, their usage during the past years was questioned following the emergence of some alarming data regarding their safety and especially the cardiovascular safety of rosiglitazone. As a result, there is often some skepticism about the current role of TZDs in T2DM management. This mainly affects rosiglitazone even leading to its withdrawal from several markets in contrast to pioglitazone, which has shown a beneficial cardiovascular profile. A comprehensive assessment of the benefit-to-risk ratio of TZDs is required in order to better understand the place of these drugs in T2DM management.

Keywords: Cardiovascular effects; Diabetes mellitus; Efficacy; Pioglitazone; Pleiotropic effects; Rosiglitazone; Safety; Thiazolidinediones.

Publication types

  • Review

MeSH terms

  • Blood Glucose / metabolism
  • Cardiovascular Diseases / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Fractures, Bone / chemically induced
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Liver / drug effects
  • Liver / pathology
  • Randomized Controlled Trials as Topic
  • Risk
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use*
  • Urinary Bladder Neoplasms / chemically induced


  • Blood Glucose
  • Hypoglycemic Agents
  • Thiazolidinediones