GLP-1受体激动剂致2型糖尿病患者胃肠道不良反应的网状Meta分析

GLP-1 receptor agonists cause gastrointestinal adverse reaction in patients with type 2 diabetes mellitus:a network meta-analysis

目的评价胰高血糖素样肽-1受体激动剂(GLP-1RA)对2型糖尿病(T2DM)患者胃肠道反应的影响。方法系统检索PubMed、Embase和Cochrane Library等数据库中自建库起至2023年10月1日GLP-1RA治疗T2DM的随机对照试验,试验组药物为一种GLP-1RA,对照组药物为安慰剂或另一种GLP-1RA。采用贝叶斯网状荟萃分析方法,探讨各GLP-1RA胃肠道不良反应发生风险,如恶心、呕吐、食欲减退、便秘、消化不良、腹泻等。结果共纳入文献45篇,涉及患者27729例。GLP-1RA引起胃肠道不良反应的总发生率为11.66%。与安慰剂相比,替尔泊肽引发恶心、腹泻、消化不良、食欲减退的风险最高,利司那肽引发呕吐的风险最高,司美格鲁肽引发便秘的风险最高。与安慰剂相比,除洛塞那肽外,其余GLP-1RA均显著增加呕吐的风险;除利司那肽外,其余GLP-1RA均显著增加腹泻的风险;除替尔泊肽、利司那肽外,其余GLP-1RA均显著增加便秘的风险;所有GLP-1RA均能显著降低食欲及增加消化不良的风险(P<0.05)。结论GLP-1RA可增加T2DM患者发生胃肠道不良反应的风险,不同GLP-1RA引发各症状的风险不同,其中替尔泊肽引发消化道症状的风险较高,值得临床关注与警惕。

AIM To evaluate the effects of glucagon-like peptide-1 receptor agonists(GLP-1RA)on gastrointestinal adverse reactions in patients with type 2 diabetes mellitus(T2DM).METHODS The databases PubMed,Embase,and Cochrane Library were systematic searched for randomized controlled trials of GLP-1RA for the treatment of T2DM from the time of construction until October 1st,2023,with one GLP-1RA as the drug in the trial arm and placebo or another GLP-1RA as the drug in the control arm.Bayesian network meta-analysis was used to explore the risk of gastrointestinal adverse reactions,such as nausea,vomiting,anorexia,constipation,dyspepsia,and diarrhea.RESULTS Forty-five papers were included,involving 27729 patients.The overall incidence of gastrointestinal adverse reactions caused by GLP-RA was 11.66%.Compared with placebo,tirzepatide caused the highest risk of nausea,diarrhea,dyspepsia,and anorexia,lixisenatide caused the highest risk of vomiting,and semaglutide caused the highest risk of constipation.Compared with placebo,all GLP-1RA except loxenatide significantly increased the risk of vomiting;all GLP-1RA except lixisenatide significantly increased the risk of diarrhea;all GLP-1RA significantly increased the risk of constipation except tirzepatide and lixisenatide;all GLP-1RA significantly decreased appetite and increased the risk of dyspepsia(P<0.05).CONCLUSION GLP-1RA significantly increased the risk of gastrointestinal adverse reactions in T2DM patients,and different drugs have different risks of various symptoms,among which tirzepatide has a higher risk of gastrointestinal symptoms,which deserves clinical attention and vigilance.