Thiazolidinediones and the Promise of Insulin Sensitization in Type 2 Diabetes
Raymond E. Soccio,1 Eric R. Chen,1 and Mitchell A. Lazar1,
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA *Correspondence: lazar@mail.med.upenn.edu
http://dx.doi.org/10.1016/j.cmet.2014.08.005
Abstract
Type 2 diabetes is caused by insulin resistance coupled with an inability to produce enough insulin to control blood glucose, and thiazolidinediones (TZDs) are the only current antidiabetic agents that function primarily by increasing insulin sensitivity. However, despite clear benefits in glycemic control, this class of drugs has recently fallen into disuse due to concerns over side effects and adverse events. Here we review the clinical data and attempt to balance the benefits and risks of TZD therapy. We also examine potential mechanisms of action for the beneficial and harmful effects of TZDs, mainly via agonism of the nuclear receptor PPARg.
Based on critical appraisal of both preclinical and clinical studies, we discuss the prospect of harnessing the insulin sensitizing effects of PPARg for more effective, safe, and potentially personalized treatments of type 2 diabetes.