胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者消化不良和厌食发生风险的Network Meta分析  

Risk of dyspepsia and anorexia due to glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus：a Network Meta-analysis

作　　者：李志霞[1] 曾宪涛[2] 柴三葆[3] 全晓驰 武珊珊[1] 杨智荣[1] 詹思延[1] 孙凤[1] 

机构地区：[1]北京大学医学部流行病与卫生统计学系,100191 [2]武汉大学中南医院循证与转化医学中心 [3]首都医科大学基础医学院

出　　处：《药物不良反应杂志》2015年第3期185-195,共11页Adverse Drug Reactions Journal

基　　金：国家自然科学基金青年科学基金（81302508）;高等学校博士学科点专项科研基金（2012000110015）

摘　　要：目的：评价胰高血糖素样肽1受体激动剂（ GLP-1 RA）致2型糖尿病（ T2DM）患者发生消化不良和厌食的风险。方法检索中国生物医学文献数据库、中国生物医学期刊目次数据库、Medline、EMbase、Cochrane library数据库和ClinicalTrials. gov网站（截至2014年5月1日），收集研究对象为T2DM患者、干预措施为GLP-1 RA与安慰剂或传统降糖药物比较、结局指标包括消化不良和厌食的随机对照试验（ RCT ），分别进行传统 Meta 分析和 Network Meta 分析，绘制各干预措施的Network Meta关系图和秩排序图。结果共纳入42个RCT，包括20916例T2DM患者和13种干预措施[7种GLP-1 RA（艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽）、5种传统降糖药（胰岛素、二甲双胍、磺脲类药物、西格列汀、噻唑烷二酮类药物）和安慰剂]。传统Meta分析显示，与安慰剂比较，总GLP-1 RA增加消化不良[比值比（ OR）=3.04，95%置信区间（CI）为1.79~5.16]和厌食（OR=2.57，95%CI为1.69~3.91）的发生风险（均P〈0.05）。Network Meta分析显示，与安慰剂比较，阿必鲁肽、艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽增加消化不良发生风险（均P〈0.05）；其中利拉鲁肽风险最大，是安慰剂的7.69倍。与胰岛素、二甲双胍、磺脲类药物、西格列汀、噻唑烷二酮类药物比较，GLP-1 RA致T2DM患者消化不良发生风险均增加；其中以利拉鲁肽发生风险最大，分别为胰岛素、二甲双胍、磺脲类药物、西格列汀、噻唑烷二酮类药物的13.58、4.17、3.85、5.00和3.70倍。与安慰剂比较，杜拉鲁肽、艾塞那肽、利拉鲁肽、他司鲁肽可增加厌食发生风险（均P〈0.05）；其中以杜拉鲁肽风险最大，是安慰剂的5.53倍；与胰岛素、磺脲类药物、噻唑烷二酮类药物、西格列汀比较（除外利西拉来与西格列汀Objective To evaluate the risk of dyspepsia and anorexia due to glucagon-like peptide-1 receptor agonist（GLP-1 RA）in patients with type 2 diabetes mellitus（T2DM）. Methods The electronic database of Chinese BioMedical Literature Database（ CBMdisc ）, Chinese Medical Current Contents（ CMCC）,Medline,EMbase,the Cochrane Library and web site of ClinicalTrials. gov were searched from inception to May 1st 2014. Those randomized controlled trials whose inclusion criteria including patients with T2DM as the research object,comparisons of GLP-1 RA and placebo or other conventional anti-diabetic drugs as the intervention measures,and dyspepsia and anorexia as the outcomes were collected. A traditional Meta-analysis and a Network Meta-analysis were used and relational graph and rank ordering figure of all the intervention measures were drawn. Results A total of 42 randomized controlled trials were enrolled into this study involving 20 916 patients with T2DM and 13 kinds of intervention measures comprised 7 kinds of GLP-1 RAs（ exenatide,exenatide release agent,liraglutide, lixisenatide,taspoglutide, albiglutide, and dulaglutide ）, 5 kinds of conventional anti-diabetic drugs （ insulin, metformin, sulfonylureas, sitagliptin, and thiazolidinediones ketones ）, and placebo. The traditional Meta-analysis showed that,compared with placebo,the whole of GLP-1 RAs could increase the risks of dyspepsia[odds ratio（OR）=3. 04,95% confidence interval（CI）：1. 79-5. 16]and anorexia （OR=2. 57,95%CI：1. 69-3. 91）and there were statistically significant differences（P 〈0. 05）. The Network Meta-analysis showed that,compared with placebo,albiglutide,exenatide,exenatide release agent, liraglutide,lixisenatide,and taspoglutide could increase the risks of dyspepsia with statistically significant differences（all P〈0. 05）and,of them,liraglutide was at the greatest risk and the risk was 7. 69（1/0. 13）times as high as that of the placebo. Compared with insulin,metformin,sulfonylureas,sitagliptin, and th

关 键 词：胰高血糖素样肽1 糖尿病 2型 消化不良 厌食 META分析 

分 类 号：R587.1[医药卫生—内分泌]