利西拉来治疗2型糖尿病的有效性及安全性的Meta分析

Efficacy and safety of lixisenatide in comparison to placebo:a metaanalysis of randomized controlled trials

目的:系统评价利西拉来与安慰剂比较治疗2型糖尿病的疗效和安全性。方法:计算机检索PubMed、EMBASE、OVID、Cochrane、CNKI、VIP、CBM数据库,查找利西拉来与安慰剂比较治疗2型糖尿病的随机对照试验(randomized controlled trial,RCT),对纳入研究进行方法学质量评价,并用RevMan 5.2软件进行Meta分析。通过Stata 12.0软件对其是否对称按Begg's法进行分析,另外通过考察单项研究对总合并效应量的影响来进行敏感性分析,以评价结论的稳健性。结果:共纳入8个RCT,随访时间≤24周的Meta分析结果显示:利西拉来在控制糖化血红蛋白(hemoglobin A1C,HbA1c)<7%[RR=1.96,95%CI(1.65,2.32),P<0.00001,Z=7.79]或≤6.5%[RR=2.70,95%CI(2.26,3.23),P<0.00001,Z=10.83]的达标率方面均优于安慰剂组。总不良反应及低血糖、注射部位反应、胃肠道反应、恶心、呕吐、头晕的发生率与安慰剂组相比,利西拉来组均高于安慰剂。头痛、腹泻的发生率两组相似,无统计学差异。所有不良反应均较轻微,绝大多数患者可以耐受。随访时间为76周时,Meta分析结果显示:利西拉来在控制糖化血红蛋白<7%[RR=1.30,95%CI(1.12,1.51),P=0.0005,Z=3.49]或≤6.5%[RR=1.41,95%CI(1.12,1.78),P=0.004,Z=2.89]的达标率方面均优于安慰剂组。总不良反应、注射部位反应、胃肠道反应、恶心、呕吐的发生率与安慰剂组相比,利西拉来组均高于安慰剂,而低血糖、腹泻两组无明显差异。结论:利西拉来可以有效控制2型糖尿病患者血糖,利西拉来主要的不良反应是低血糖、注射部位反应、胃肠道反应、恶心、呕吐、头晕、头痛、腹泻,但不良反应较轻微,因此可以用来治疗2型糖尿病,但远期结果有待高质量、大样本、长期随访的临床研究予以验证。

AIM：To estimate the efficacy and tolerability of lixisenatide in comparison to placebo in the treatment of type 2diabetes.METHODS：PubMed,EMBASE,OVID,Cochrane,CNKI,VIP,CBM were searched and randomized controlled trials（RCT）of lixisenatide vs.placebo in treating type 2diabetes were collected.The quality of included randomized controlled trials（RCTs）was assessed and then analyzed by the software RevMan5.2.The potential publication bias was performed by Stata 12.0soft.Sensitivity analyses were used in the treatment course.RESULTS：Eight RCTs were ultimately identified.The results of meta-analyses showed that the proportion of patients that achieved an HbA1 c〈7%or≤6.5% was significantly greater in lixisenatide group than that in placebo group,there was statistical significance.The number of total adverse events,hypoglycemia,injection sites reactions,gastrointestinal disorders,nausea,vomiting,dizziness events in lixisenatide group was significantly lower than that in control group,there was statistical significance.Most of the adverse events reported were mild to moderate in intensity.CONCLUSION：The results of meta-analyses indicate that lixisenatide treatment for type 2diabetes is effective.The major adverse of lixisenatide were hypoglycemia,injection site reactions,gastrointestinal disorders,nausea,vomiting,dizziness,headache,diarrhea.Although it may increase the risk of the adverse events,which reported were mild to moderate in intensity,lixisenatide appears to be an effective treatment for type 2diabetes and a long-term study in large scale with high quality is required to confirm its longterm outcomes.