Efficacy and safety of empagliflozin combined with metformin in treating patients with type 2 diabetes mellitus: a Meta-analysis
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摘要:目的 系统评价恩格列净(EMPA)联合二甲双胍(MET)治疗2型糖尿病的疗效和安全性。方法 计算机检索PubMed、Cochrane图书馆、EMBase、万方数据库和中国期刊全文数据库等, 收集恩格列净联合二甲双胍治疗2型糖尿病的随机对照试验(RCT), 同时检索纳入文献的参考文献。由2名评价员独立进行文献质量评价和资料提取后，采用RevMan5.3软件进行Meta分析。结果 共纳入5项RCT, 合计2 244例2型糖尿病患者。Meta分析结果显示, EMPA+MET组在降低患者糖化血红蛋白水平方面显著优于MET组[加权均数差(WMD)=-0.47, 95%置信区间(CI)为-0.72~-0.22, P < 0.05]; EMPA+MET组与MET组患者在不良事件发生率[相对危险度(RR)=0.98, 95%CI为0.90~1.05, P=0.55]、低血糖发生率(RR=0.88, 95%CI为0.50~1.56, P=0.67)和泌尿系感染发生率(RR=1.22, 95%CI为0.91~1.63, P=0.19)方面相当; EMPA+MET组患者生殖系感染发生率(RR=4.12, 95%CI为2.31~7.34, P < 0.001)显著高于MET组。结论 EMPA联合MET治疗2型糖尿病的总体安全性较好，临床联合使用恩格列净和二甲双胍时仍应注意监测患者的生殖系感染情况。Abstract:Objective To systematically evaluate the efficacy and safety of empagliflozin (EMPA) combined with metformin (MET) in treating patients with type 2 diabetes mellitus.Methods PubMed, the Cochrane Library, EMbase, Wanfang Data and CNKI were searched to collect the randomized controlled trials (RCTs) on empagliflozin plus metformin in treatment of patients with type 2 diabetes mellitus, and references of included studies were also retrieved. Two reviewers independently screened studies, extracted data, and assessed the methodological quality. All data were analyzed by Review Manager 5.3.Results Five studies including 2 244 patients were included. The results of Meta-analysis showed that when compared to MET groups, EMPA plus MET showed better effect on the improvement of HbA1c levels [weighted mean difference (WMD)=-0.47, 95% confidence interval (CI)=-0.72~-0.22, P < 0.05]. There were no signi cant differences between EMPA plus MET groups and MET groups in the incidence of adverse events (RR=0.98, 95%CI=0.90~1.05, P=0.55), hypoglycemic incidence (RR=0.88, 95%CI=0.50~1.56, P=0.67) and incidence of urinary tract infections (RR=1.22, 95%CI=0.91~1.63, P=0.19). There was a signi cant difference between EMPA plus MET groups and MET groups in the incidence of genital infections (RR=4.12, 95%CI=2.31~7.34, P < 0.001).Conclusion Based on this rexiew, EMPA plus MET has good efficacy and overall safety in treating patients with type 2 diabetes mellitus, but physicians should pay more attention to genital infections when they adopt this treatment method.
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表 1 纳入研究的基本特征
纳入研究 组别 n 干预措施 HbA1c/% 体质量/kg 研究周期/周 结局指标 FeRRannini E等, 2013[8] T1 166 EMPA10mg+MET 7.88±0.74 89.6±15.0 78 ①②③④ T2 166 EMPA25 mg+MET 7.91±0.78 89.5±16.2 C 56 MET 8.15±0.95 85.8±15.6 Rosenstock J等, 2013[9] T1 71 EMPA10mg+MET 7.90±0.70 87.9±14.4 12 ①②③④ T2 70 EMPA25 mg+MET 8.10±0.80 90.5±16.9 C 71 PBO+MET 8.00±0.70 87.7±15.7 Haring H U等, 2014[10] T1 217 EMPA10mg+MET 7.94±0.79 81.6±18.5 24 ①②③④ T2 213 EMPA25 mg+MET 7.86±0.87 82.2±19.3 C 207 PBO+MET 7.90±0.88 79.7±18.6 Merker L等, 2015[11] T1 172 EMPA10mg+MET 7.90±0.80 83.6±18.5 76 ①②③④ T2 152 EMPA25 mg+MET 7.90±0.90 84.4±20.4 C 138 PBO+MET 7.80±0.80 81.5±19.0 Ross S等, 2015[12] T1 220 EMPA10mg+MET 7.84±0.75 89.2±19.0 16 ①②③④ T2 218 EMPA25 mg+MET 7.73±0.79 89.4±19.0 C 107 PBO+MET 7.69±0.72 90.1±18.4 T: 研究组; C: 对照组; ①: HbA1c水平变化; ②: 低血糖发生率; ③: 泌尿系感染发生率; ④: 生殖系感染发生率。 
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表 2 纳入研究的方法学质量评价
纳入研究 随机方法 分配隐藏 盲法 失访/退出 方法学质量 FeRRannini E等, 2013 仅描述随机 未描述 否 是 B Rosenstock J等, 2013 是 是 是 是 A Haring H U等, 2014 是 是 是 是 A Merker L等, 2014 仅描述随机 未描述 否 是 B Ross S等, 2015 仅描述随机 未描述 未描述 是 B
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