胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者头疼和眩晕的网状Meta分析

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目的:使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂(GLP-1 RAs)类降糖药对2型糖尿病(T2DM)患者头疼和眩晕的影响.方法:系统检索Medline、Embase、Clinical trials和Cochrane数据库中(截止2017年6月23日)比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验(RCT),采用贝叶斯网状Meta分析对纳入的研究进行分析.结果:共纳入100项RCTs,包括15种干预措施:8种GLP-1 RAs类降糖药(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、索玛鲁肽)、安慰剂、2种二肽基肽酶4(DPP-4)抑制剂(西格列汀和维格列汀)和4种传统降糖药(胰岛素、二甲双胍、磺脲类、噻唑烷二酮类).网状Meta分析结果显示:与胰岛素相比,艾塞那肽(OR=1.35,95% CI:1.13 ~ 1.60)、利拉鲁肽(OR=1.35,95% CI:1.12 ~ 1.62)、利西拉来(OR=1.59,95% CI:1.22 ~2.06)和他司鲁肽(OR=1.78,95% CI:1.33 ~ 2.37)致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险(OR的取值范围为1.56-2.56).此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽.结论:艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证.“,”Objective:To systematically review the effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on headache and dizziness among type 2 diabetes (T2DM) patients.Methods:Medline,Embase,Clinical trials and Cochrane library were searched from inception through June 23,2017 to identify randomized clinical trials (RCTs) assessing safety of GLP-1 RAs versus placebo or other anti-diabetic drugs in T2DM.Network Meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of headache and dizziness.Results:In the study,100 RCTs were included,including 15 treatments:8 GLP-1 RAs (exenatide,exenatide-long-release-agent,liraglutide,lixisenatide,taspoglutide,albiglutide,dulaglutide and semaglutide),placebo,2 dipeptidyl peptidase-4 inhibitors (sitagliptin and vildagliptin) and 4 traditional anti-diabetic drugs (insulin,metformin,sulfonylureas and thiazolidinediones ketones (TZD)).Compared with insulin,exenatide,liraglutide,lixisenatide and taspoglutide significantly increased the incidence of headache,with OR of 1.35 (95% CI:1.13-1.60),1.35 (95% CI:1.12-1.62),1.59 (95% CI:1.22-2.06) and 1.78 (95% CI:1.33-2.37),respectively.Significant lowering effects on dizziness were found when liraglutide and exenatide versus placebo,insulin,TZD (range of ORs:1.56-2.56).The result from the network Meta-analysis based on Bayesian theory could be used to rank all the treatments included,which showed that taspoglutide ranked third with maximum risk on headache,liraglutide ranked first with maximum risk on dizziness.Conclusion:Exenatide-long-release-agent and taspoglutide were associated with significantly increasing effect on headache,tiraglutide was associated with significantly increasing effect on dizziness.
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