GLP-1类糖尿病药物的胰腺炎风险引起监管机构重视

两个月前，发表在《美国医学会杂志》上的一篇有关一些重磅糖尿病药物与癌症风险相关的研究论文引发出一些新的问题。一个月之前，FDA声称正在就该项研究中提及的两款糖尿病药物（默沙东的西他列汀及百时美施贵宝和阿斯利康的艾塞那肽）以及包括诺和诺德重磅炸弹级药物利拉鲁肽在内的其它药物进行审查。目前，如Pharmalot报道，一支安全监管组织对FDA收集的不良反应数据进行了分析，发现与早先的糖尿病治疗药物相比，这些糖尿病药物有更多的胰腺炎和胰腺癌报道。

安全用药研究所(ISMP)分析发现，胰高血糖素样肽-1（GLP-1）类药物的这种疾病报道量大约高25倍。作为独特类型的糖尿病药物，二肽基肽酶-4抑制剂药物西他列汀连同胰高血糖素样肽-1药物艾塞那肽和利拉鲁肽发生胰腺炎的报道几率最大。但对早期礼来与勃林格殷格翰的利拉利汀及百时美施贵宝和阿斯利康的沙格列汀来说，虽仍属上述二肽基肽酶-4抑制剂药物，但这些药物的胰腺炎报道率却较低。

这些报道并不意味着这些药物与不良事件报道存在因果关系。FDA的不良反应数据库依赖于医生、患者与公司的报道。有些病例因未被报道而不会进入数据库。并且报道本身也可能有误导性，因为没有办法知道个别不良反应病例是否就是源于这类药物的治疗还是简单的纯属巧合。就二肽基肽酶-4抑制剂药物和胰高血糖素样肽-1药物来说，它们经常被加到二甲双胍中作为控制患者血糖的治疗标准，所以使用这些药物的患者可能已经处在胰腺炎高风险的境地。

另外，由于这些报道是自发的，所以不能太过依赖于这些不同类型药物相互对比的报道。但较高的不良事件报道数量会引起关注，并且FDA通常会基于这些报道来调查药物。

如Pharmalot报道，安全用药研究所热衷于号召对这类药物进行跟踪研究。“我认为这类药物在将来会有问题，”安全用药研究所的Thomas Moore说。“如果这种结果在更大患者人群范围内被证实，那整个的这类药物就会存在问题。”

与此同时，自《美国医学会杂志》发布这项研究后，制药商及医生对研究数据提出了质疑。百时美施贵宝和默沙东均为它们的药物进行了辩护。两家公司已在它们的药品标签上增加了胰腺炎病例的警告信息。我们只能观望FDA在完成其审查后的反应。

与糖尿病相关的拓展阅读：

• Diabetes Care：糖尿病视网膜病和微量白蛋白尿可预测T2DM患者大量白蛋白尿和肾功能减退
• NEJM：糖尿病治疗领域的进展与不足
• JAMA：研究支持对糖尿病患者进行更强力的抗血小板治疗
• Obes Surg：减重手术可能不能“治愈”糖尿病
• Cell Metab:新的血清标志物提前数年预测糖尿病风险
• Circulation：精氨酸酶抑制剂治疗糖尿病患者并发症
更多信息请点击：有关糖尿病更多资讯

Safety watchdog flags GLP-1 drugs for pancreatitis reports to FDA
Two months ago, a study published in the Journal of the American Medical Association raised some new questions about cancer risks linked with some big diabetes drugs. One month ago, the FDA said it was reviewing data on the two drugs flagged in that study--Merck's ($MRK) Januvia, and Bristol-Myers Squibb ($BMY) and AstraZeneca's ($AZN) Byetta--as well as other drugs, including Novo Nordisk's ($NVO) blockbuster Victoza. Now, as Pharmalot reports, a safety watchdog group has analyzed the FDA's adverse event data, finding more reports of pancreatitis and pancreatic cancer for these drugs compared with older treatments.
The Institute for Safe Medication Practices (ISMP) analysis found that reports of these maladies were about 25 times higher for the GLP-1 class. As individual drugs, Januvia, a DPP-4 inhibitor, along with GLP-1 drugs Byetta and Victoza, were found to have the greatest odds of pancreatitis reports. The odds were lower, but still above those for older treatments, for DPP-4 inhibitors Eli Lilly ($LLY) and Boehringer Ingelheim's Tradjenta/Trajenta; and Bristol-Myers Squibb and AstraZeneca's Onglyza.
These numbers don't necessarily mean that there's a causal relationship between the drugs and the adverse event reports. The FDA database depends on reports from doctors, patients and companies. Some cases never make it into the database because they go unreported. And reports themselves can be misleading, because there's no way of knowing whether a particular case actually stemmed from drug treatment or simply coincided with it. In the case of the GLP-1 and DPP-4 drugs, they're often added to metformin as patients' blood-sugar control flags, so the people who use them may already be at higher risk of pancreatitis.
Read more: Safety watchdog flags GLP-1 drugs for pancreatitis reports to FDA - FiercePharma http://www.fiercepharma.com/story/safety-watchdog-flags-glp-1-drugs-pancreatitis-reports-fda/2013-04-18#ixzz2Slyj3sWp
Subscribe at FiercePharma
Plus, because the reports are voluntary, one can't lean too much on them in comparisons among different drug brands. Still, higher numbers are cause for concern, and the FDA often investigates drugs based on them.
But as Pharmalot reports, the ISMP is sufficiently concerned to call for follow-up study. "I think the future of the whole class is in question," the ISMP's Thomas Moore told the blog. "[I]f results are confirmed in a broader patient population, it raises questions about the entire class of drugs."
Meanwhile, since the JAMA study hit, drugmakers and doctors poked holes in the data. Bristol-Myers and Merck have both defended their drugs. Both already carry label warnings about pancreatitis cases. We'll have to wait and see what the FDA says when its review is complete.
Read more: Safety watchdog flags GLP-1 drugs for pancreatitis reports to FDA - FiercePharma http://www.fiercepharma.com/story/safety-watchdog-flags-glp-1-drugs-pancreatitis-reports-fda/2013-04-18#ixzz2SlyluHla
Subscribe at FiercePharma