2型糖尿病患者在磺酰脲类药物治疗基础上加用DPP4抑制剂的疗效和安全性Meta分析

Efficacy and safety of dipeptidyl peptidase-4 inhibitors combined with sulfonylureas in type 2 diabetes mellitus:a Meta-analysis

目的系统评价二肽基肽酶4(DPP4)抑制剂联合磺酰脲类药物治疗2型糖尿病(T2DM)的疗效和安全性。方法计算机检索PubMed,Cochrane,EMbase数据库获得符合标准的研究,检索时间为建库至2018年1月15日。由2名作者独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Stata14.1和RevMan5.3软件进行统计分析并计算相对危险度(RR)和加权均数差(WMD),并评价研究间的异质性和发表偏倚。结果最终纳入19个随机对照研究,共9119例患者。与对照组(使用磺酰脲类药物,或加入其他降糖药物)相比,联合组(DPP4抑制剂联合磺酰脲类药物)可显著改善血糖水平[糖化血红蛋白(HbA1c)减少0.72%,空腹血糖减少0.84mmol/L,餐后2h血糖减少1.88mmol/L],增加体质量(增加了0.70kg)。然而,联合组低血糖事件发生率显著增加(RR=1.60,95%CI:1.38~1.85)。亚组分析显示与对照组比较,短期类(疗程小于24周)两药联合方案(RR=1.08,95%CI:0.47~2.46)和低剂量DPP4抑制剂联合磺酰脲类药物方案(RR=1.33,95%CI:0.92~1.94)未显著性增加低血糖事件发生率。结论DPP4抑制剂联用磺酰脲类药物能够有效改善T2DM患者血糖水平,但显著性增加患者低血糖事件发生率和体质量。采用这种治疗方案时应及时对磺酰脲类药物和DPP4抑制剂剂量进行调整。

Objective To investigate the efficacy and safety of dipeptidyl peptidase-4(DDP4)inhibitor combined with sulfonylureas in type 2 diabetes mellitus(T2DM).Methods Databases including the PubMed,Cochrane Library,Embase were searched to collect relevant studies from inception to 15 January 2018.Two reviewers independently screened literature,extracted data,and assessed the methodological quality of included studies,then Stata14.1 and RevMan 5.3 software were used to calculate risk ratio(RR)and weighted mean difference(WMD)with 95%confidence interval(CI).Heterogeneity across studies and publication bias were tested.Results A total of 19 trials including 9 119 patients were analysed.Compared with the control group,DPP4 inhibitor combination with sulfonylurea(combined group)could significantly improve blood glucose levels(HbA1c,FPG,2 h PPG decreased 0.72%,0.84 mmol/L,1.88 mmol/L respectively),and increased body weight(increased by 0.70 kg).However,the incidence of hypoglycemic events(RR=1.60,95%CI:1.38-1.85)in combination group also significantly in creased.Subgroup analysis showed that,combination regimen in a short-term(less than 24 weeks)(RR=1.08,95%CI:0.47-2.46)and the regimen of low-dose DPP4 inhibitor combined with sulfonylurea(RR=1.33,95%CI:0.92-1.94)did not increase the incidence of hypoglycemic events when compared with control group.Conclusion DPP4 inhibitor combined with sulfonylurea can effectively improve blood glucose levels in T2DM patients,but significantly increase the incidence of hypoglycemic events and body mass.Clinicians need to adjust sulfonylureas dose and the dose of DPP4 inhibitor in a timely manner.