Rosiglitazone in the prevention of diabetes and cardiovascular disease: dream or reality?

Results of the recently published DREAM trial seemingly demonstrate that the PPAR-gamma agonist rosiglitazone is effective in the prevention of diabetes. However, a more detailed inspection of the trial shows that rosiglitazone is masking rather than preventing the progression to diabetes. This questionable effect was achieved at the price of unnecessarily treating approximately five subjects who would remain nondiabetic anyway for each case of "prevented" diabetes, with all the associated costs and risks. The trial also raises the unexpected possibility that rosiglitazone may substantially increase the risk of cardiovascular events, which would be particularly harmful in the high-risk patients with diabetes. This possibility is further supported by the results of several recent meta-analyses. In addition, these serious safety concerns should be carefully weighed against the weak evidence of benefit which, so far, is limited to laboratory endpoints. Therefore, rather than extending the use of rosiglitazone to the prevention of diabetes, the DREAM trial calls in question the safety of this drug as such in any patient and casts some doubt upon the whole class of PPAR-gamma agonists. With respect to its wide use in clinical practice, the potential risks of rosiglitazone warrant careful investigation and, in the meantime, this drug should be used with caution.