Stulc Tomas, Ceska Richard
3rd Department of Internal Medicine, 1st School of Medicine, Charles University, Prague, Czech Republic.
Med Sci Monit. 2008 Apr;14(4):RA45-7.
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.
最近公布的DREAM试验结果似乎表明，PPAR-γ激动剂罗格列酮在预防糖尿病方面是有效的。然而，对该试验进行更详细的审视后发现，罗格列酮是在掩盖而非预防糖尿病的进展。这种可疑的效果是以不必要地治疗大约五名无论如何都不会患糖尿病的受试者为代价换来的，每一例“预防”的糖尿病都有这样的代价，还伴随着所有相关的成本和风险。该试验还引发了一个意想不到的可能性，即罗格列酮可能会大幅增加心血管事件的风险，这对糖尿病高危患者尤其有害。最近几项荟萃分析的结果进一步支持了这一可能性。此外，这些严重的安全问题应与有限的获益证据仔细权衡，到目前为止，获益证据仅限于实验室终点指标。因此，DREAM试验并非是在呼吁扩大罗格列酮在预防糖尿病方面的应用，而是对该药物在任何患者中的安全性提出了质疑，并对整个PPAR-γ激动剂类药物产生了一些怀疑。鉴于其在临床实践中的广泛应用，罗格列酮的潜在风险值得仔细研究，与此同时，使用该药物时应谨慎。
