Walker Simon R, Komenda Paul, Khojah Suhail, Al-Tuwaijri Wafa, MacDonald Kerry, Hiebert Brett, Tangri Neil, Nadurak Stewart W D, Ferguson Thomas W, Rigatto Claudio, Tangri Navdeep
Chronic Disease Innovation Center, Winnipeg, MB, Canada.
Nephron. 2017;136(2):85-94. doi: 10.1159/000454683. Epub 2017 Feb 9.
Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population.
We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2). We extracted study characteristics, participants' baseline characteristics, and safety outcomes from eligible studies. We performed a random effects meta-analysis to summarize the change in HbA1C and the relative risk of cardiovascular events in patients with T2DM and CKD. We also collected data on hypoglycemia, other serious adverse events, and mortality.
We reviewed 12 studies with 4,403 patients with CKD and 239 on dialysis, finding a mean weighted decline in HbA1C of -0.48 (95% CI -0.61 to -0.35) with DPP-4 inhibitor therapy compared to placebo. DPP-4 inhibitors did not result in any additional adverse events, hypoglycemic episodes, or increased mortality. Restricting to studies with low risk of bias did not alter these findings.
DPP-4 inhibitors can lower HbA1C without increasing the risk of cardiovascular or other major adverse events in patients with CKD. Few studies reported critical adverse events such as heart failure and hypersensitivity. If compared with other oral antiglycemic drugs, the effect of DPP-4 inhibitors is limited; however, their low risk of hypoglycemia may favor their use in patients with CKD.
This systematic review of DPP-4 inhibitors in CKD suggests that they reduce HbA1C by about 0.5%. Furthermore, there was not any increase in the risk for significant adverse events. More research is needed to determine the safety and efficacy of DPP-4 inhibitors in CKD.
慢性肾脏病（CKD）在2型糖尿病（T2DM）患者中很常见，并且限制了治疗选择。二肽基肽酶-4（DPP-4）抑制剂是一类新型的口服降糖药物，在普通人群中已知是安全有效的。
我们检索了Cochrane、EMBASE和PubMed数据库，检索时间从各数据库建立至2015年3月。我们纳入了分析DPP-4药物在肾功能减退（估计肾小球滤过率<60 mL/min/1.73 m²）个体中的疗效（糖化血红蛋白[A1C]变化）和安全性的随机对照试验。我们从符合条件的研究中提取研究特征、参与者的基线特征和安全性结局。我们进行了随机效应荟萃分析，以总结T2DM和CKD患者糖化血红蛋白的变化以及心血管事件的相对风险。我们还收集了低血糖、其他严重不良事件和死亡率的数据。
我们回顾了12项研究，共4403例CKD患者和239例透析患者，发现与安慰剂相比，DPP-4抑制剂治疗使糖化血红蛋白平均加权下降-0.48（95%CI -0.61至-0.35）。DPP-4抑制剂未导致任何额外的不良事件、低血糖发作或死亡率增加。限于偏倚风险低的研究并未改变这些结果。
DPP-4抑制剂可降低CKD患者的糖化血红蛋白，而不增加心血管或其他主要不良事件的风险。很少有研究报告心力衰竭和过敏等严重不良事件。与其他口服降糖药物相比，DPP-4抑制剂的效果有限；然而，其低血糖风险低可能有利于在CKD患者中使用。
这项对CKD患者中DPP-4抑制剂的系统评价表明，它们可使糖化血红蛋白降低约0.5%。此外，重大不良事件风险未增加。需要更多研究来确定DPP-4抑制剂在CKD中的安全性和疗效。
