二肽基肽酶Ⅳ抑制剂治疗2型糖尿病合并慢性肾脏病患者的心肾结局

Cardiovascular and renal outcomes of DPP-4 inhibitors in patients with type 2 diabetes and chronic kidney disease

慢性肾脏病(CKD)是2型糖尿病(T2DM)患者最常见的合并症,也是心血管疾病的独立危险因素。大多数口服降糖药及其代谢产物由肾脏排泄,肾功能不全时半衰期延长,造成药物在体内蓄积,增加低血糖及其他相关不良反应风险。合并CKD的T2DM患者在选择降糖药时,应充分考虑肾功能情况,优选具有肾脏获益证据、经肾脏排泄少、低血糖风险低的药物。二肽基肽酶Ⅳ抑制剂(DPP-4i)作用机制独特,降糖疗效确切,不增加体重和低血糖风险,且使用简便,临床应用越来越广泛。4种DPP-4i开展的大型心血管结局研究(CVOT)在不同肾功能状态的T2DM患者中,评估了药物的疗效和安全性。不同DPP-4i虽降糖疗效相似,但药物特点及心肾结局存在一定差异。本综述基于CVOT,归纳比较了不同肾功能状态患者使用DPP-4i的心血管安全性和肾脏相关结局,并对DPP-4i的潜在肾脏获益及机制进行探讨,以期为合并CKD的T2DM患者的治疗提供循证参考。

Chronic kidney disease(CKD)is the most common complication of patients with type 2 diabetes(T2 DM)and is an independent risk factor for cardiovascular disease.Most oral glucose-lowering drugs and their metabolites are excreted via kidneys;extension of the half-life,drug accumulation induced hypoglycemia and other adverse reactions are seen in patients with renal impairment.The renal conditions of patients with T2 DM and CKD should be considered when prescribing glucose-lowering drugs;the drugs with clear renal benefits,low hypoglycemia risk and those are excreted via kidneys the least are preferred.Dipeptidyl peptidase-4 inhibitor(DPP-4 i)has been commonly used in clinic due to its unique mechanism of action,glycemic control effect,low risk for hypoglycemia and weight gain,as well as simplicity to use.The four major cardiovascular outcome trials(CVOTs)also evaluated the efficacy and safety of DPP-4 is in patients with T2 DM and different renal conditions.Although the glycemic control effects of the four DPP-4 is are similar,the characteristic of each DPP-4 i differs from each other,as well as the cardiovascular and renal outcomes in patients treated with different DPP-4 is also differ.This review aimed to summarize and compare the data regarding cardiovascular and renal outcomes in patients with T2 DM and different renal conditions who received DPP-4 i in the CVOTs;as well as to discuss the mechanisms of action underlying the renal benefits of DPP-4 i in order to provide evidence on the treatment of DPP-4 i in patients with T2 DM and CKD.