钠-葡萄糖共转运蛋白2抑制剂对2型糖尿病患者酮症酸中毒影响的Meta分析

Effects of sodium-glucose cotransporter 2 inhibitors on ketoacidosis in patients with type 2 diabetes mellitus:a meta-analysis

目的系统评价钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)对2型糖尿病(T2DM)患者发生酮症酸中毒(DKA)风险的影响。方法计算机检索美国国立医学图书馆数据库(Pubmed)、医学文摘数据库(Embase)和Cochrane循证医学数据库(Cochrane Library)从建库至2021年11月30日收录的有关SGLT2i治疗T2DM患者的随机对照试验(RCT)。提取纳入文献的样本量、研究对象年龄、体重指数(BMI)、发生DKA情况、使用降糖药种类及时间。采用RevMan 5.4软件进行Meta分析,二分类变量用相对危险度(RR)值及95%CI作为效应量。结果共纳入36个RCT涉及69760例T2DM患者,共发生DKA事件139个,其中SGLT2i组106个,对照组33个。与对照组相比,SGLT2i组发生DKA的风险更高(RR=2.70,95%CI 1.83~3.98,P<0.001)。亚组分析显示,与各自的对照组相比,年龄>60岁(RR=2.72,95%CI 1.83~4.04,P<0.001)、BMI≥31 kg/m2(RR=2.72,95%CI 1.82~4.06,P<0.001)、用药时间>52周(RR=2.72,95%CI 1.83~4.04,P<0.001)接受SGLT2i治疗的T2DM患者发生DKA的风险更高;在药物种类亚组中,卡格列净(RR=4.81,95%CI 1.69~13.63,P=0.003)、埃格列净(RR=4.09,95%CI 1.10~15.19,P=0.040)比对照组发生DKA的风险更高。结论SGLT2i会增加T2DM患者发生DKA的风险。而且年龄越大、BMI越高、用药时间越长,发生DKA的风险越高,并且DKA的高风险与药物种类有关。

Objective To systematically evaluate whether sodium-glucose cotransporter receptor-2 inhibitors(SGLT2i)increase the risk of diabetic ketoacidosis(DKA)in adults with type 2 diabetes mellitus(T2DM).Methods Randomized controlled trials(RCT)of SGLT2i in patients with T2DM included in Pubmed,Embase and Cochrane Evidence Based Medicine databases were searched from the establishment of the databases to November 30,2021.Data such as sample size,age of subjects,body mass index(BMI),occurrence of DKA,type and time of hypoglycemic drugs used were extracted.Revman 5.4 software was used for meta-analysis.The risk ratio(RR)value and 95%CI were used as effect variables for dichotomous variables.Results A total of 36 RCT involving 69760 T2DM patients were included,and 139 DKA events occurred,including 106 DKA events in the SGLT2i group and 33 DKA events in the control group.Compared with the control group,SGLT2i group had a higher risk of DKA(RR=2.70,95%CI 1.83-3.98,P<0.001).Subgroup analysis showed that T2DM patients with age>60 years(RR=2.72,95%CI 1.83-4.04,P<0.001),BMI≥31 kg/m^(2)(RR=2.72,95%CI 1.82-4.06,P<0.001)and medication duration>52 weeks(RR=2.72,95%CI 1.83-4.04,P<0.001)who received SGLT2i had a higher risk of DKA compared with their respective control groups.In the subgroups of drug types,the risk of DKA was higher in canagliflozin(RR=4.81,95%CI 1.69-13.63,P=0.003)and ertugliflozin(RR=4.09,95%CI 1.10-15.19,P=0.04)than in the control group.Conclusions This study suggests that SGLT2i increase the risk of DKA in patients with T2DM.Moreover,the older the age,the higher the BMI,and the longer the duration of receiving SGLT2i,the higher the risk of developing DKA,and the risk of DKA is also related to the type of medication.