SGLT-2抑制剂致成人2型糖尿病患者糖尿病酮症酸中毒风险的Meta分析

Effects of sodium-glucose cotransporter 2 inhibitor on ketoacidosis in adults with type 2 diabetes mellitus:A Meta-analysis

目的对钠—葡萄糖协同转运蛋白2(SGLT-2)抑制剂致成人2型糖尿病(T2DM)患者糖尿病酮症酸中毒(DKA)风险进行系统Meta分析。方法检索美国国立医学图书馆数据库、医学文摘数据库、Cochrane循证医学数据库从建库至2023年12月31日收录SGLT-2抑制剂治疗T2DM患者的随机对照试验。提取纳入文献的样本量、患者性别、年龄、体质量指数、发生DKA情况、治疗时间及药物种类。使用RevMan5.4版软件进行Meta分析,二分类变量以相对危险度(RR)值及95%CI作为效应量。结果最终共纳入26篇文献65176例T2DM患者,其中SGLT-2抑制剂治疗(观察组)37021例,对照组28155例;共发生DKA事件139例,观察组DKA事件发生率为0.29%(106/37021),对照组DKA事件发生率为0.12%(33/28155),观察组发生DKA风险显著高于对照组(RR=2.71,95%CI 1.84~3.97,P<0.001)。进一步亚组分析提示SGLT-2抑制剂组中年龄>60岁(RR=2.73,95%CI 1.84~4.05,P<0.001)、体质量指数≥31 kg/m^(2)(RR=2.73,95%CI 1.82~4.07,P<0.001)、治疗时间>52周(RR=2.73,95%CI 1.84~4.05,P<0.001)、使用卡格列净(RR=4.82,95%CI 1.70~13.64,P=0.003)、埃格列净(RR=4.10,95%CI 1.11~15.20,P=0.040)发生DKA风险均较对照组明显升高。结论成人T2DM患者应用SGLT-2抑制剂会增加DKA风险,且年龄越大、体质量指数越高、治疗时间越长发生DKA的风险就越高,另外DKA发生风险也与药物种类有关。

Objective To conduct a systematic meta-analysis of the risk of ketoacidosis(DKA)in adults with type 2 diabetes mellitus(T2DM)caused by SGLT-2 inhibitors.Methods Randomized controlled trials(RCT)of SGLT-2 inhibitors in adults with T2DM included in PubMed,Embase and Cochrane Library were searched from the establishment of the databases to December 31,2023.Data such as sample size,age of subjects,body mass index,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 26 RCT involving 65176 T2DM patients were included,including 37021 T2DM patients in the SGLT-2 group and 28155 T2DM patients in the control group,and 139 DKA events occurred.The incidence of DKA events in the SGLT-2 group was 0.29%(106/37021),while in the control group it was 0.12%(33/28155).Compared with the control group,SGLT-2 group had a higher risk of DKA(RR=2.71,95%CI 1.84~3.97,P<0.001).Subgroup analysis showed that T2DM patients with age>60 years(RR=2.73,95%CI 1.84~4.05,P<0.001),body mass index≥31 kg/m^(2)(RR=2.73,95%CI 1.82~4.07,P<0.001)and medication duration>52 weeks(RR=2.73,95%CI 1.84~4.05,P<0.001)who received SGLT-2 inhibitors 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=4.82,95%CI 1.70~13.64,P=0.003)and ertugliflozin(RR=4.10,95%CI 1.11~15.20,P=0.040)than in the control group.Conclusions SGLT-2 inhibitors can increase the risk of DKA in adults with T2DM.Moreover,the older the age,the higher body mass index,and the longer the duration of receiving SGLT-2 inhibitors,the higher the risk of developing DKA,and the risk of DKA is also related to the type of medication.