Scheen André J
University of Liège, CHU Sart Tilman, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine , (B35), B-4000 Liege 1 , Belgium +32 4 3667238 ; +32 4 3667068 ; andre.scheen @ chu.ulg.ac.be.
Expert Opin Drug Saf. 2015 Apr;14(4):505-24. doi: 10.1517/14740338.2015.1006625. Epub 2015 Jan 29.
Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy a growing place in the armamentarium of drugs used for the management of hyperglycemia in type 2 diabetes, although some safety concerns have been raised in recent years.
An updated review providing an analysis of available safety data (meta-analyses, randomized controlled trials, observational cohort and case-control studies and pharmacovigilance reports) with five commercialized DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin). A special focus is given to overall safety profile; pancreatic adverse events (AEs) (acute pancreatitis, pancreatic cancer); overall cardiovascular safety (myocardial infarction and stroke); congestive heart failure concern and finally, safety in special populations (elderly, renal impairment).
The good tolerance/safety profile of DPP-4 inhibitors has been largely confirmed, including in more fragile populations (elderly, renal impairment) with almost no increased risk of infection or gastrointestinal AEs, no weight gain and a minimal risk of hypoglycemia. Although an increased risk of acute pancreatitis and pancreatic cancer was suspected, the complete set of available data appears reassuring so far. Cardiovascular safety of DPP-4 inhibitors has been proven but an unexpected increased risk of heart failure has been reported which should be confirmed in ongoing trials and better understood. Further postmarketing surveillance is recommended.
二肽基肽酶-4(DPP-4)抑制剂(格列汀类药物)在用于治疗2型糖尿病高血糖的药物库中所占地位日益重要,尽管近年来出现了一些安全性问题。
一篇更新的综述,分析了五种已上市的DPP-4抑制剂(西他列汀、维格列汀、沙格列汀、阿格列汀、利格列汀)的现有安全性数据(荟萃分析、随机对照试验、观察性队列研究、病例对照研究及药物警戒报告)。特别关注总体安全性概况;胰腺不良事件(急性胰腺炎、胰腺癌);总体心血管安全性(心肌梗死和中风);充血性心力衰竭问题,最后是特殊人群(老年人、肾功能损害患者)的安全性。
DPP-4抑制剂良好的耐受性/安全性概况已得到很大程度的证实,包括在较为脆弱的人群(老年人、肾功能损害患者)中,几乎没有感染或胃肠道不良事件风险增加、无体重增加且低血糖风险极小。尽管曾怀疑急性胰腺炎和胰腺癌风险增加,但目前整套现有数据似乎令人安心。DPP-4抑制剂的心血管安全性已得到证实,但有报告称出现了意外的心力衰竭风险增加情况,这应在正在进行的试验中得到确认并更好地理解。建议进一步开展上市后监测。