The TDZ's seem always to be in the news,the bad news. First, Rezulin was taken off the market because of liver toxicity.Next, the issue of Avandia increasing the risk of heart attack arose and arose and arose and seemingly the issue will never be settled. Now Actos is being accused of increasing the risk of bladder cancer.
Most recently the FDA has taken action to strictly limit its use and make it fairly difficult for a new patient to be prescribed that drug. In Europe, apparently it will be taken off the market and folks currently taking that medication will have to be switched to something else.
An interesting action taken by the FDA is to require GSK to commission an independent "re-adjudication" of the RECORD study. This was the clinical trial with 4447 patients in which rosiglitazone (Avandia) was compared with the combination of metformin and a sulfonylurea and concluded that results was inconclusive in regard to what everyone was interested, namely cardiovascular outcomes. Somehow the FDA expects more analysts looking at the data will turn the inconclusiveness into some conclusions. More likely it won't but then maybe everyone can move on and worry about some other adverse effect of something else.
FDA's reasoning seems to be that if these new adjudicators can get an answer then the TIDE trial ( still another trial that the optimists think will settle the issue) will not have to be taken off of hold. The FDA put TIDE on full clinical hold.
Several years ago when one attended the infomercials with food ( AKA drug company sponsored CME -dinners) several speakers could talk about little else but the PPAR receptors and after much time and money was aimed at doing something really good therapeutically with those receptors little was accomplished. See here for some comments by a research insider about the PPAR story.
Early on in the Avandia kerfuffle I went on and on about the issue of "small"increases in relative risk and how is relatively easy to tell a big thing from a little thing but how difficult it is for epidemiology to tell a little thing from nothing at all. The original Nissen and Wolski paper talks about a relative risk of 1.43. With risks of 3 and 4 there is typically little to argue about. With RRs less than 2 it seems we go round and round for a long time before the combatants run out of stream.