SGLT2抑制剂治疗2型糖尿病肾脏安全性的Meta分析

Renal safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: a meta-analysis

目的评价钠-葡萄糖共转运蛋白2 (SGLT2)抑制剂治疗2型糖尿病(T2DM)对肾脏安全性的影响。方法通过检索PubMed、 Embase、 OVID、 Cochrane Library、 Web of Science、中国知网、万方、维普等数据库及临床试验注册网站,查找SGLT2抑制剂与安慰剂或其他类降血糖药比较治疗T2DM的随机对照试验(RCT),采用RevMan 5.3对肾小球滤过率(eGFR)、血肌酐(SCr)、尿白蛋白与肌酐比值(UACR)等肾功能指标以及肾功能损害、急性肾功能衰竭的发生率进行Meta分析。结果共纳入38个RCT,包括20 163例T2DM患者。当疗程≤26周时,与安慰剂组比较, SGLT2抑制剂高剂量组eGFR显著降低(WMD=-9.03, 95%CI:-1.56～-0.31, P=0.004, I^2=33%)、 SCr显著增高(WMD=0.70, 95%CI:0.09～1.30, P=0.02, I^2=0%);而两个剂量组与阳性对照组相比均无显著差异(P>0.05)。当疗程≥48周时, SGLT2抑制剂两个剂量组eGFR和SCr改变与安慰剂组均相似(P> 0.05);与阳性对照组比较,两个剂量组eGFR均显著增高、 SCr显著降低(P <0.05)。SGLT2抑制剂两个剂量组UACR与安慰剂组无显著差异(P> 0.05);疗程≥48周时,与阳性对照组比较,高剂量组UACR显著降低(WMD=-20.05, 95%CI:-37.79～-2.32, P=0.03, I2=0%)。SGLT2抑制剂组肾功能损害和急性肾功能衰竭发生率与安慰剂组和阳性对照组比较均无显著差异(P> 0.05)。结论 SGLT2抑制剂治疗T2DM患者引起肾功能损害、急性肾功能衰竭的风险与安慰剂或阳性药相当,在持续治疗中对肾脏的安全性较好。

AIM To evaluate the renal safety of sodium-glucose cotransporter 2(SGLT2)inhibitors in patients with type 2 diabetes mellitus(T2 DM).METHODS PubMed,Embase,OVID,Cochrane Library,Web of Science,CNKI,Wanfang and VIP database and clinical trial registration sites were searched to collect the literatures on rand omized controlled trials(RCTs)of SGLT2 inhibitors compared with placebo or positive control agents.The meta-analysis was conducted by RevMan 5.3 software about the outcomes of renal safety such as estimated in glomerular filtration rate(eGFR),serum creatinine(SCr),urinary albumin to creatinine ratio(UACR),the incidence of renal impairment and acute renal failure.RESULTS Thirty-eight RCTs were included,including 20 163 patients with T2DM.During less than 26 weeks,a greater reduction in eGFR(WMD=-9.03,95%CI:-1.56--0.31,P=0.004,I^2=33%)and a greater increase in SCr(WMD=0.70,95%CI:0.09-1.30,P=0.02,I^2=0%)were observed in high dose group of SGLT2 inhibitors compared with placebo group,whereas no significant differences in eGFR and SCr between the two dose groups of SGLT2 inhibitors and positive control group(P>0.05).During more than 48 weeks,there were no significant differences in e GFR and SCr between SGLT2 inhibitors groups and placebo group(P>0.05).Compared with the positive control group,e GFR was significantly increased and SCr was significantly decreased in the two dose groups(P<0.05).There were no significant differences in UACR between the two dose groups of SGLT2 inhibitors and placebo group(P>0.05).Compared with the positive control group,UACR was significantly lower in the high dose group during more than 48 weeks(WMD=-20.05,95%CI:-37.79--2.32,P=0.03,I^2=0%).In the incidence of renal impairment and acute renal failure,there were no significant differences between the SGLT2 inhibitors groups and the placebo group or the positive control group(P>0.05).CONCLUSION The incidence of renal impairment and acute renal failure of SGLT2 inhibitors in treatment of patients with T2DM is similar with placebo or positive control agents,and the renal safety of SGLT2 is better in continuous treatment.