Troglitazone: the discovery and development of a novel therapy for the treatment of Type 2 diabetes mellitus.
Prior to the introduction of troglitazone, it had been more than 30 years since the last significant improvement in antidiabetic therapy. In view of the pressing need for more effective oral agents for the treatment of Type 2 diabetes mellitus, troglitazone was granted priority review by the FDA and was launched in the USA in 1997. The first of the thiazolidinedione insulin sensitizing agents, troglitazone was quickly followed by rosiglitazone and pioglitazone. The glitazones proved to be effective not only in lowering blood glucose, but also to have beneficial effects on cardiovascular risk. Troglitazone was subsequently withdrawn because of concerns about hepatotoxicity, which appears to be less of a problem with rosiglitazone and pioglitazone. Recent insights into the molecular mechanism of action of the glitazones, which are ligands for the peroxisome proliferator-activated receptors, open the prospect of designing more effective, selective and safer antidiabetic agents. This document will review the history of troglitazone from discovery through clinical development.
Parker
Janice C
JC
Pfizer Global Research & Development, Groton Laboratories, 8220-0375, Eastern Point Road, Groton, CT 06340, USA. janice_c_parker@groton.pfizer.com
D002839:Chromans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone