Thiazolidinediones TZD

Thiazolidinediones TZD

MOJTABA   MALEK

Associate Professor of Endocrinology

Tehran University of Medical Sciences

Endocrine research center(firozgar)

  Agenda:

14. TZDs Overview
14. Pioglitazone Studies
14. Rosiglitazone Studies
14. TZDs and Cardiovascular Risks
14. TZDs Fracture Data
14. TZDs and Cancer
14. Summary

TZDs Action

14. Selective binding at the  peroxisome proliferator activated receptor- gamma (PPAR-g),which is found in adipose tissue, skeletal muscle, pancreatic beta-cells, vascular endothelium ,macrophages and the liver.
14.  Decrease in insulin resistance at peripheral sites and in the liver that results in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
14. Pioglitazone [Actos] :  15/30/45 mg
14. Rosiglitazone [Avandia]:  4mg/bid
14. Troglitazone (Rezulin) : Withdrawn from the U.S market in 2000 due to hepatotoxicity.
14. Peak Concentration : 2 to 4 hours
14. Initial Response :  4 weeks

14. Dose adjustment : NOT necessary in

                      renal insufficiency or elderly

14. Should not be used in:

     active liver disease or  serum ALT > 2.5 times

DREAM trial

14. A decrease in diabetes in subjects with IFG or IGT who were treated with rosiglitazone was reported.
14. Metformin and thiazolidinediones had similar efficacy as monotherapy.
14. The cost and side effects of thiazolidinediones make them less appealing as initial therapy and do not suggest for diabetes prevention.