GLP-1受体激动剂治疗2型糖尿病合并肾损伤患者的疗效和安全性:一项Meta分析

Therapeutic efficacy and safety of GLP-1 receptor agonists in type 2 diabetic patients with renal impairment:a Meta-analysis

目的:评价胰高血糖素样肽-1受体激动剂(GLP-1RAs)在2型糖尿病(T2DM)合并肾损伤患者中的疗效和安全性,为该类药物的临床应用提供循证参考。方法:检索Medline、Embase、Cochrane Library、中国知网(CNKI)和万方数据库,查找有关GLP-1RAs治疗T2DM合并肾损伤患者的随机对照试验(RCT)。按照纳入与排除标准筛选文献,进行方法学质量评价之后提取相关资料,应用RevMan 5.3统计软件进行Meta分析。结果:最终纳入7项RCT,共计1 755例T2DM合并肾损伤患者。疗效方面,GLP-1RAs与胰岛素类似物或二肽基肽酶4抑制剂降低糖化血红蛋白的效应相当,但优于安慰剂,且该疗效在中重度肾损伤患者中比终末期肾病患者更佳;与对照组相比降低体质量[MD=-1.75,95%CI=(-2.18,-1.32),P<0.01]和降压作用[收缩压:MD=-7.79,95%CI=(-10.83,-4.74),P<0.01;舒张压:MD=-2.92,95%CI=(-4.79,-1.05),P=0.002]均有显著性差异;但降低空腹血糖和调节脂质代谢方面未见统计学差异。安全性方面,GLP-1RAs组与对照组致低血糖和肾损伤事件的发生率[RR=1.28,95%CI=(0.56,2.96),P=0.560;RR=0.85,95%CI=(0.44,1.62),P=0.620]无统计学差异,然而GLP-1RAs组胃肠道不良反应的发生率显著高于对照组(P<0.01)。结论:对于T2DM合并肾损伤患者,GLP-1RAs具有确切的降糖、减重和降压作用,而在终末期肾病患者中疗效降低;用药期间不增加低血糖和肾损伤风险,但应注意预防胃肠道不良反应的发生。

OBJECTIVE To evaluate the efficacy and safety of glucagon like peptide-1 receptor agonists(glp-1 ras)in patients with type 2 diabetes mellitus(T2 DM)complicated with renal injury, and to provide evidence-based reference for the clinical application of such drugs.METHODS By searching Medline, Embase, Cochrane Library, CNKI and Wanfang databases, randomized controlled trials(RCTs)about GLP-1 RAs in T2 DM patients with renal impairment were collected.Literature was screened according to inclusion and exclusion criteria, and relevant information was extracted after methodological quality evaluation.Meta-analysis was performed by using RevMan 5.3 statistical software.RESULTS A total of 7 RCTs were included, involving 1 755 T2 DM patients with renal impairment.In terms of efficacy, GLP-1 RAs were equivalent to insulin analogues or dipeptidyl peptidase-4 inhibitors in reducing hemoglobin A1 c, but better than placebo, and the effect was better in patients with moderate to severe renal impairment than in patients with end-stage renal disease;compared with the control group, there were significant differences in weight loss[MD=-1.75,95% CI=(-2.18,-1.32),P<0.01]and blood pressure reduction[systolic pressure: MD=-7.79,95% CI=(-10.83,-4.74),P<0.01;diastolic pressure: MD=-2.92,95% CI=(-4.79,-1.05),P=0.002];while no statistically significant differences were found in improving fasting plasma glucose or blood lipids.In terms of safety, there was no significant difference in the incidence of hypoglycemia and renal impairment between GLP-1 RAs group and the control[RR=1.28,95% CI=(0.56,2.96),P=0.560,RR=0.85,95% CI=(0.44,1.62),P=0.620],while the incidence of gastrointestinal adverse reactions in GLP-1 RAs group was significantly higher than that in control group(P<0.01).CONCLUSION In T2 DM patients with renal impairment, GLP-1 RAs have definite effects on reducing blood glucose, weight and blood pressure, but theirs therapeutic effect is reduced in patients with end-stage renal disease.The risk of hypoglycemia and renal impairment is not increased during the treatment period, but attention should be paid to prevent gastrointestinal adverse reactions.