title: Thiazolidinedione safety.
abstract: BACKGROUND
  Thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk-benefit analysis to determine what role TZDs should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed.
  
  
  METHODS
  This review provides a comprehensive overview of the literature from 2000 onward reporting the known side effects of rosiglitazone and pioglitazone, with commentary on the quality of the data available, putative mechanism of each side effect and clinical significance. Finally, a perspective on the future of the TZDs as a class is provided.
  
  
  CONCLUSIONS
  The current TZDs are first-generation, non-specific activators of peroxisome proliferator-activated receptor (PPAR) gamma, resulting in a wide array of deleterious side effects that currently limit their use. However, the development of highly targeted selective PPAR gamma modulators (SPPARγMs) and dual PPAR gamma/alpha agonists is on the horizon.
authors.affiliation: Tufts University, Division of Endocrinology, Diabetes and Metabolism, 800 Washington St #268, Boston, MA 02111, USA. JKung@tuftsmedicalcenter.org
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kung
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D050723:Fractures, Bone / Q000139:chemically induced; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects; D008269:Macular Edema / Q000139:chemically induced; D009203:Myocardial Infarction / Q000139:chemically induced; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D045162:Thiazolidinediones / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
chemical_list: D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones