Thiazolidinediones and Clinical Diabetes Management: New Challenges for the Fall of 2007
AbstractThree thiazolidinediones (TZDs) have been introduced into clinical use in the United States. These compounds are nuclear transcription activators that affect dozens of different genes. Due to the unique coactivator and corepressor proteins that associate and dissociate with the PPAR-gamma protein/TZD complex, no two of these compounds should be expected to have exactly the same pattern of gene activation or suppression.1–3 Troglitazone was withdrawn from the market due to what appears to have been a unique idiosyncratic end stage liver disease that was not observed with pioglitazone or rosiglitazone. The event rate for this fatal hepatotoxicity was approximately 1:35,000 exposed patients.4 Based upon the fact that two safer TZDs were available, the FDA suggested that troglitazone be withdrawn from the market. In an open-labeled conversion study conducted after the withdrawal of troglitazone, subjects were randomly converted from troglitazone to either rosiglitazone or pioglitazone.5 No difference was noted in hemoglobin A1c depending on which TZD was used. However, the conversion from troglitazone to pioglitazone was associated with more than a 15% fall in LDL concentration, while converting from troglitazone to rosiglitazone caused little change in LDL concentration.
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