Lessons from the glitazones: a story of drug development

Troglitazone, the first in the thiazolidinediane class of oral hypoglycaemi c agents, was launched in the USA in March, 1997. It reached Europe later t hat year, only to be withdrawn within weeks on the grounds of liver toxicit y. Meanwhile it went on to generate sales of over $2 billion in the. USA, a nd caused at least 90 cases of liver failure (70 resulting in death or tran splantation) before it was withdrawn in March, 2000. Rosiglitazone and piog litazone reached the US market in 1999:as first-line agents to be used alon e 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 re stricted to oral combination therapy. How should we use the glitazones? And how did they achieve blockbuster status without any clear evidence of adva ntage over existing therapy?