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[ADA2012]吡格列酮的心血管获益与癌症风险
——Guntram Schernthaner专访
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作者:G.Schernthaner 2012/6/12 11:04:00    加入收藏
内容概要:Schernthaner博士:我认为吡格列酮仍然是一个有意义的药物。当然,吡格列酮有骨折和心衰相关水潴留等严重不良反应。关于吡格列酮与膀胱癌风险的数据还不明确,不过最新的来自凯泽永久医疗集团(Kaiser Permanente)的大型数据库提示我们,目前没有证据显示吡格列酮与膀胱癌风险有关。

  Guntram Schernthaner  奥地利维也纳大学附属Rudolfstiftung医院内科主任、第32届EASD年会主席

  <International Diabetes>: There were several controversial topics this year at ADA. One of them was the PPAR agonist debate. Could you give us your opinion on what you thought of that debate?
  Prof. Schernthaner: In my opinion, pioglitazone is still an interesting drug. Of course there are a number of critical side effects such as bone fractures and increased water retention associated with heart failure. The data concerning bladder cancer are unclear but the latest very large database from Kaiser Permanente is telling us there is no signal. One should be very careful with all of these observational studies and it is more important that bladder cancer is not a very common cancer. Other cancer forms are much more common in type 2 diabetic patients and there are at least five or six very good papers already published or coming out soon that are telling us that several more common cancers in type 2 diabetic patients are prevented by the use of TZDs in general and in particular by pioglitazone. The problem is also that you should select patients for the use of pioglitazone; it is not the drug for everyone. It is certainly is the relatively best drug in patients already presenting with cardiovascular disease such as stroke, myocardial infarction and acute coronary syndrome.  

  《国际糖尿病》:今年的ADA年会有几个有争议的话题。一个就是关于PPAR激动剂的讨论。你怎么看这场讨论?
  Schernthaner博士:我认为吡格列酮仍然是一个有意义的药物。当然,吡格列酮有骨折和心衰相关水潴留等严重不良反应。关于吡格列酮与膀胱癌风险的数据还不明确,不过最新的来自Kaiser 大型数据库的结果提示我们,目前没有证据显示吡格列酮与膀胱癌风险有关。对于所有的一系列观察性研究,我们应当非常小心。更为重要的是膀胱癌并不是非常常见的癌症。其他癌症在T2MD患者更为常见。至少有五、六篇质量非常高的已经发表或即将发表的论文提示我们,总体上来讲应用TZD类药物(尤其是吡格列酮)可以预防T2DM患者发生其他几种更为常见的癌症。另外,我们需要选择适合应用吡格列酮的患者,并不是每例患者都适合应用吡格列酮。当然,在已有卒中、心梗和急性冠脉综合征的T2DM患者,吡格列酮是最好的药物。
  <International Diabetes>:  What about the potential for cardiovascular risk using pioglitazone?
  Prof. Schernthaner: There is no risk at all for increasing risk. There is a risk for heart failure which we showed in the PROactive Study but interestingly enough this increase in heart failure was not associated with an increased mortality. This can most likely be explained by most heart failure associated with pioglitazone being different from the classical heart failure so there are several studies in the literature, even with rosiglitazone, telling us that the function of the heart is not changed but that it is even improved by the TZDs and it is only the water retention that causes the problem with heart failure in patients already with some degree of compromised heart function.

  《国际糖尿病》:应用吡格列酮时发生心血管事件的潜在风险如何?
  Schernthaner博士:吡格列酮不增加心血管事件发生风险。吡格列酮增加心衰风险,这是从PROactive试验中观察到的,但是非常有趣的是,心衰风险的增加与死亡率增加无相关关系。这很可能是由于绝大多数的吡格列酮相关心衰与经典的心衰有所不同。因此,有几项研究发现,即使是应用了吡格列酮,患者的心脏功能仍然没有变化,甚至心功能还有所改善,只是在一些心功能有某种程度受损的患者中,水潴留才导致了心衰的发生。

  <International Diabetes>:  On the basis of the PROactive six-year extension studies, what is the significance of assessing the cardiovascular effects of pioglitazone?
  Prof. Schernthaner: It is the best drug relatively concerning the durability of glucose lowering; better than sulfonylureas and even better than metformin. Of course, these observational studies at the end of the randomized study always have limitations but nevertheless, in the six-year extension there was no signal for increased bladder cancer risk. However there was also no durability of the cardiovascular benefit but this is difficult to evaluate because you don’t have precise information as to how many patients are still on the drug or have stopped the drug. Probably, you have to use the drug continuously to have the benefit so there probably won’t be a long-lasting effect if you stop the drug, which makes sense. We recently published the data from the EUREXA Study in The Lancet and it is now online. The first author and senior author is Baptist Gallwitz and what we could show was that exenatide bi-daily is much better than the sulfonylurea, glimepiride, for a period of about 4 ? years. Even in the EUREXA Study we have seen some increase of HbA1c in patients with a mean duration of five years only so probably we have to look further as to whether pioglitazone is superior, inferior or equal to GLP-1 agonists concerning durability of glycemic control.


  《国际糖尿病》:基于PROactive试验的六年延长研究结果,你认为评价吡格列酮心血管效应的意义何在?
  Schernthaner教授:从降糖作用持久性的角度来说,吡格列酮是最好的药物,优于磺脲类药物,甚至比二甲双胍还要好。当然,观察性研究与随机研究相比总是存在一些局限性,但是PROactive试验六年延长研究未显示吡格列酮增加膀胱癌发生风险。不过,也没有证据显示吡格列酮有持续的心血管获益,但是心血管获益比较难以评价,因为对于有多少患者还在应用吡格列酮或已经停用吡格列酮,研究者并没有确切的信息。要想获益需要持续用药,如果停药的话,可能就不会有持久的益处,这听起来是合理的。
  我们最近在《柳叶刀》杂志上发表了EUREXA研究的数据,该数据同时在线发表。该文章的第一作者是Baptist Gallwitz。EUREXA研究显示,艾塞那肽每日两次要明显优于磺脲类药物格列美脲,此作用共维持了4.5年。即使是在EUREXA研究中,我们也观察到了患者的HbA1c有所升高,平均治疗5年。我们可能需要进一步比较吡格列酮与GLP-1受体激动剂在持久控制血糖方面的表现。
 

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