Lessons from the glitazones: a story of drug development.
Troglitazone, the first in the thiazolidinedione class of oral hypoglycaemic agents, was launched in the USA in March, 1997. It reached Europe later that year, only to be withdrawn within weeks on the grounds of liver toxicity. Meanwhile it went on to generate sales of over $2 billion in the USA, and caused at least 90 cases of liver failure (70 resulting in death or transplantation) before it was withdrawn in March, 2000. Rosiglitazone and pioglitazone reached the US market in 1999 as first-line agents to be used alone or in combination with other drugs, but in Europe the same dossiers were used one year later to apply for a limited licence as second-line agents restricted to oral combination therapy. How should we use the glitazones? And how did they achieve blockbuster status without any clear evidence of advantage over existing therapy?
Gale
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Diabetes/Metabolism, Medical School Unit, Southmead Hospital, 10HA 5NB, Bristol, UK. Edwin.Gale@bristol.ac.uk
D016907:Adverse Drug Reaction Reporting Systems; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002839:Chromans / Q000008:administration & dosage / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D004359:Drug Therapy, Combination; D005060:Europe; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017093:Liver Failure / Q000139:chemically induced; D000077205:Pioglitazone; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014481:United States
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone; D000077205:Pioglitazone