罗格列酮安全性再评价:一项基于随机对照研究、队列研究、病例对照研究及病例报告的系统评价

Re-evaluation on safety of rosiglitazone: A systematic review based on randomized controlled trials,cohort studies,case-control studies and case reports

目的:评价与其他抗糖尿病口服药物相比,罗格列酮治疗2型糖尿病患者的安全性。方法:按照检索策略在EMbase、MEDLINE、The Cochrane library等6个数据库中进行电子检索,并人工进行补充检索。按纳入排除标准进行筛选,对纳入文献进行偏倚风险评估,并使用Revman 5.3软件进行统计学Meta分析。结果:共纳入63篇研究,其中随机对照试验17篇。研究结果显示,罗格列酮组的总不良反应发生率与其他口服糖尿病药物相比无显著差异,然而RCT研究结果提示罗格列酮组因不良反应退出的比例高于非TZD类药物组,但低于吡格列酮组。对于心脑血管不良反应发生率,RCT研究和队列研究结果都支持罗格列酮与其他糖尿病药物相比无统计学意义,但病例对照研究结果认为罗格列酮暴露组心脑血管不良反应发生率高于未暴露组。罗格列酮组的低血糖发生率与二甲双胍组无显著差异,且低于磺脲类。RCT研究结果提示罗格列酮组体质量升高的患者比例和水肿发生率高于其他口服降糖药。队列研究结果显示罗格列酮组的骨折发生率高于其他药物,但低于吡格列酮。对于膀胱癌的发病率,队列研究结果显示罗格列酮组发病率低于吡格列酮组以及其他非TZD类糖尿病药物组,而病例对照研究却得到了相反的结果。结论:应用罗格列酮治疗2型糖尿病,总体不良反应发生率不高于其他口服降糖药,且尚无确切证据证明该药致心脑血管事件的风险高于其他抗糖尿病药物,但应对其水肿、体质量增加、骨折的风险加以预防,并警惕其致肿瘤风险。

OBJECTIVE To evaluate the safety of rosiglitazone on type 2 diabetes mellitus patients compared with other oral antidiabetic agents. METHODS We searched EMbase, MEDLINE, The Cochrane library, VIP, CNKI and WAN FANG database were searched. After methodology quality evaluation and data extraction, the software RevMan 5.3 was used to perform Meta analysis. RESULTS Seventeen randomized controlled studies, twenty-two cohort studies, thirteen case-control researches and eleven case reports were included. The results showed that there was no significant difference in total adverse reaction rate between rosiglitazone group and other oral diabetes drugs, but RCT results suggested that the exit rate due to adverse reactions iwas higher in rosiglitazone groups than in non-TZDs groups, but lower than in piglitazone groups. RCT and cohort studies results showed no statistical significance in the incidence of cardiovascular reactions between rosiglitazone and other antidiabetic drugs, while the result of case-e control studies revealed that the incidence of cardioa-cerebrovascular adverse effects in rosiglitazone-exposed group was higher than thoseat of non rosiglitazone-exposed groups. There was no significant difference in the incidence of hypoglycemia between rosiglitazone group and metformin group. The results of RCT showed that the proportion of patients with weight gain and the incidence of edema in rosiglitazone group were higher than those of other oral antidiabetic drugs. The result of cohort study showed that fracture incidence of rosiglitazone group was higher than that of other drugs, but lowerless than that of pioglitazone. For the incidence of bladder cancer, cohort studies showed that incidence of rosiglitazone group iwas lower than that of pioglitazone group and non TZDs diabetes drug group although case-control studies yielded contradictory results. CONCLUSION When used againstin treatment of t type 2 diabetes, rosiglitazone does not result in higher adverse reactions rate overall than those of other oral antidiabetic drugs, and there is no conclusive evidence to prove the cardiovascular risk of rosiglitazone compared with other antidiabetic drugs. However, it is necessary to prevent the risk of edema, weight gain, and fracture, and to be aware of the risk of cancer.