SGLT2抑制剂联合二甲双胍治疗2型糖尿病的安全性和有效性的Meta分析

Efficacy and Safety of Metformin Plus SGLT2 Inhibitors for Type 2 Diabetes:A Meta-Analysis

目的:系统评价钠葡萄糖共转运子2(SGLT2)抑制剂联合二甲双胍(MET)治疗2型糖尿病(T2DM)的疗效及安全性。方法:计算机检索PubMed、The Cochrane Library、EMbase、CNKI、WanFang Data、VIP和CBM,收集SGLT2抑制剂联合MET与单用MET比较治疗T2DM的随机对照试验,检索时限均为建库至2013年11月,并追溯纳入研究的参考文献。由两位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后,采用RevMan 5.1软件进行Meta分析。结果:共纳入9个RCT,3 422例患者。Meta分析结果显示:SGLT2抑制剂联合MET组较单用MET组能更有效地改善糖化血红蛋白水平[WMD=-0.51%,95%CI(-0.61,-0.41),P<0.000 01]、空腹血糖水平[WMD=-1.21mmol/L,95%CI(-1.46,-0.95),P<0.000 01],减轻体重[WMD=-2.07kg,95%CI(-2.40,-1.73),P<0.000 01],降低收缩压水平[WMD=-2.89mmHg,95%(-4.33,-1.45),P<0.000 01]、舒张压水平[WMD=-1.61mmHg,95%CI(-2.55,-0.67),P=0.000 8];增加了发生生殖系统感染的风险[RR=2.34,95%CI(1.45,3.78),P=0.000 5],但在发生低血糖的风险[RR=0.96,95%CI(0.58,1.60),P=0.89]、泌尿系统感染的风险[RR=1.37,95%CI(0.97,1.95),P=0.08]、常见不良反应的风险[RR=1.12,95%CI(0.99,1.26),P=0.07]及至少发生一次严重不良事件的风险[RR=1.09,95%CI(0.73,1.62),P=0.69]方面差异无统计学意义。结论:SGLT2抑制剂联合MET是一种安全且有效的治疗T2DM的降糖方法。上述结论尚有待开展更多大样本、高质量研究予以证实。

Objective：To assess the efficacy and safety of metformin plus SGLT2 inhibitors in treating type 2diabetes mellitus.Methods：Based on the principles and methods of Cochrane systematic,we searched the Cochrane Library,Pubmed,Embase,CNKI,Wanfang Data,VIP,and CBM from the date of establishment of the databases to November 2013.The bibliographies of the included studies were searched,too.Two reviewers screened the randomized controlled trials（RCTs）according to the inclusion and exclusion criteria,extracted the data,assessed the quality and conducted meta-analysis with Revman 5.1software.Results：A total of 9RCTs were included.Compared with metformin monotherapy,SGLT2 inhibitors plus metformin was associatedwith more reduction in HbA1clevel（MD=-0.51,95%CI[-0.61,-0.41],P0.000 01）,more reduction in FPG level（MD=-1.21,95%CI[-1.46,-0.95],P0.000 01）,more weight loss（MD=-2.07,95%CI[-2.40,-1.73],P0.000 01）,more reduction in systolic pressure level（MD=-2.89,95%CI[-4.33,-1.45],P0.000 01）,more reduction in diastolic pressure level（MD=-1.61,95%CI[-2.55,-0.67],P=0.000 8）,and higher risk of reproductive tract infection（%）（RR=2.34,95%CI[1.45,3.78],P=0.0005）,but was not associated with the higher risk of the incident hypoglycaemic episodes（RR=0.96,95%CI[0.58,1.60],P=0.89）,and nor the higher risk of incident UTI（%）（RR=1.37,95%CI[0.97,1.95],P=0.08）,nor the higher risk of most common adverse events（RR=1.12,95%CI[0.99,1.26],P=0.07）,and nor the higher risk of at least one serious adverse event（RR=1.09,95%CI[0.73,1.62],P=0.69）.Conclusion：SGLT2inhibitors plus metformin is safe and effective for hyperglycemia treatment in T2 DM.The above conclusion should be verified by more large-scale high-quality studies in future.