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Trends Endocrinol Metab. 2012 May;23(5):205-15. doi: 10.1016/j.tem.2012.03.001. Epub 2012 Apr 17.

Thiazolidinediones and PPARγ agonists: time for a reassessment.

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Unité Mixte de Recherche 1087, Institut National de la Santé et de la Recherche Médicale (INSERM), Nantes 44000, France.


Thiazolidinediones (TZDs) are anti-diabetic drugs that act as insulin sensitizers and are used in the management of type 2 diabetes mellitus. TZDs, which are ligands for the transcription factor peroxisome proliferator-activated receptor PPARγ, have a wide spectrum of action, including modulation of glucose and lipid homeostasis, inflammation, atherosclerosis, bone remodeling and cell proliferation. Randomized clinical trials have demonstrated the efficacy and durability of the anti-hyperglycemic action of TZDs, and have suggested that the TZD pioglitazone also exerts cardioprotective action. However, the clinical use of TZDs is limited by the occurrence of several adverse events, including body-weight gain, congestive heart failure, bone fractures and possibly bladder cancer. Therefore, there is an unmet need for the development of new safer PPARγ-modulating drugs.

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