Toronto General Hospital Research Institute, UHN, Toronto, ON, Canada.
Department of Physiology and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Nephrol Dial Transplant. 2020 Jan 1;35(Suppl 1):i3-i12. doi: 10.1093/ndt/gfz230.
The rationale for using sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) has evolved over the last decade. Due to the effects on glucosuria and body weight loss, SGLT2 inhibitors were originally approved for glycemic control in T2D. Since glucosuria is attenuated in chronic kidney disease (CKD) Stages 3-5, initial regulatory approval for SGLT2 inhibitor use was limited to patients with T2D and preserved estimated glomerular filtration rate. Over time, however, it has become increasingly apparent that these therapies have a variety of important pharmacodynamic and clinical effects beyond glycemic lowering, including antihypertensive and antialbuminuric properties, and the ability to reduce glomerular hypertension. Importantly, these sodium-related effects are preserved across CKD stages, despite attenuated glycemic effects, which are lost at CKD Stage 4. With the completion of cardiovascular (CV) outcome safety trials-EMPA-REG OUTCOME, CANVAS Program and DECLARE TIMI-58-in addition to reductions in CV events, SGLT2 inhibition consistently reduces hard renal endpoints. Importantly, these CV and renal effects are independent of glycemic control. Subsequent data from the recent CREDENCE trial-the first dedicated renal protection trial with SGLT-2 inhibition-demonstrated renal and CV benefits in albuminuric T2D patients, pivotal results that have expanded the clinical importance of these therapies. Ongoing trials will ultimately determine whether SGLT2 inhibition will have a role in renal protection in other clinical settings, including nondiabetic CKD and type 1 diabetes.
在过去的十年中，钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂在 2 型糖尿病（T2D）患者中的应用依据不断发展。由于其对糖尿和体重减轻的影响，SGLT2 抑制剂最初被批准用于 T2D 的血糖控制。由于慢性肾脏病（CKD）3-5 期的糖尿减轻，SGLT2 抑制剂最初的监管批准仅限于 T2D 和估计肾小球滤过率保留的患者。然而，随着时间的推移，越来越明显的是，这些治疗方法除了降低血糖外，还具有多种重要的药效学和临床作用，包括降压和减少尿蛋白作用，以及降低肾小球高血压的能力。重要的是，尽管在 CKD 4 期时失去了降糖作用，但这些与钠相关的作用在 CKD 各期仍然保留。随着心血管（CV）结局安全性试验-EMPA-REG OUTCOME、CANVAS 计划和 DECLARE TIMI-58 的完成，除了 CV 事件减少外，SGLT2 抑制还可一致降低肾脏硬终点。重要的是，这些 CV 和肾脏作用独立于血糖控制。最近的 CREDENCE 试验的后续数据-首次专门针对 SGLT-2 抑制的肾脏保护试验-显示出在白蛋白尿 T2D 患者中具有 CV 和肾脏获益，这些关键结果扩大了这些治疗方法的临床重要性。正在进行的试验最终将确定 SGLT2 抑制在其他临床环境（包括非糖尿病 CKD 和 1 型糖尿病）中的肾脏保护作用。
