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达格列净治疗慢性肾脏病。

Dapagliflozin for the treatment of chronic kidney disease.

机构信息

Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Japan.

出版信息

Expert Rev Endocrinol Metab. 2022 Jul;17(4):275-291. doi: 10.1080/17446651.2022.2099373. Epub 2022 Jul 13.

Abstract

INTRODUCTION

Sodium-dependent glucose cotransporter 2 (SGLT2) is a glucose transporter expressed on the proximal tubular cells, where it reabsorbs glucose from the glomerular filtrate. SGLT2 inhibitors (SGLT2is), initially developed as an antidiabetic drug, have recently attracted considerable attention because they have cardiorenal protective effects. Among SGLT2is, dapagliflozin was the first to demonstrate the renoprotective effect in patients with and without diabetes and has been approved for chronic kidney disease (CKD) treatment.

AREAS COVERED

This review covers the pharmacological characteristics and the clinical efficacy and safety profiles of dapagliflozin, including comparison with other SGLT2is and risk modification strategies.

EXPERT OPINION

In DAPA-CKD, dapagliflozin reduced the primary outcome (≥50% estimated glomerular filtration rate [eGFR] decline, end-stage kidney disease [ESKD], or renal or cardiovascular [CV] death) by 39% in CKD patients. This beneficial effect was consistent across prespecified subgroups, including those based on the presence of diabetes. Dapagliflozin also decreased the CV composite outcome and all-cause death by 29% and 31%, respectively. Although an increased risk of adverse events such as ketoacidosis and volume depletion has been reported, the robust renal and CV benefits of dapagliflozin are expected to outweigh potential risks. SGLT2is, including dapagliflozin, will constitute the mainstay of CKD treatment.

摘要

简介

钠-葡萄糖协同转运蛋白 2(SGLT2)是一种在近端肾小管细胞中表达的葡萄糖转运蛋白,它从肾小球滤过液中重吸收葡萄糖。SGLT2 抑制剂(SGLT2is)最初被开发为一种抗糖尿病药物,最近因其具有心脏和肾脏保护作用而引起了广泛关注。在 SGLT2is 中,达格列净是第一个在有或没有糖尿病的患者中证明具有肾脏保护作用的药物,并已被批准用于慢性肾脏病(CKD)的治疗。

涵盖领域

这篇综述涵盖了达格列净的药理学特性以及临床疗效和安全性概况,包括与其他 SGLT2is 的比较以及风险修正策略。

专家意见

在 DAPA-CKD 中,达格列净使 CKD 患者的主要结局(估计肾小球滤过率[eGFR]下降≥50%、终末期肾病[ESKD]或肾脏或心血管[CV]死亡)降低了 39%。这种有益的效果在预先指定的亚组中是一致的,包括基于是否存在糖尿病的亚组。达格列净还分别降低了 CV 复合结局和全因死亡的风险 29%和 31%。尽管有报道称会增加酮症酸中毒和容量不足等不良事件的风险,但达格列净对肾脏和 CV 的显著益处预计将超过潜在风险。SGLT2is,包括达格列净,将成为 CKD 治疗的主要方法。

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