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.
Decrease in insulin resistance at peripheral sites and in the liver that results in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Pioglitazone [Actos] : 15/30/45 mg
Rosiglitazone [Avandia]: 4mg/bid
Troglitazone (Rezulin) : Withdrawn from the U.S market in 2000 due to hepatotoxicity.
Peak Concentration : 2 to 4 hours
Initial Response : 4 weeks
Dose adjustment : NOT necessary in
renal insufficiency or elderly
Should not be used in:
active liver disease or serum ALT > 2.5 times
A decrease in diabetes in subjects with IFG or IGT who were treated with rosiglitazone was reported.
Metformin and thiazolidinediones had similar efficacy as monotherapy.
The cost and side effects of thiazolidinediones make them less appealing as initial therapy and do not suggest for diabetes prevention.