Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA; email:
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
Annu Rev Physiol. 2021 Feb 10;83:503-528. doi: 10.1146/annurev-physiol-031620-095920. Epub 2020 Nov 16.
SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose-dependent and -independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是一类抗高血糖药物，可预防伴有或不伴有 2 型糖尿病及保留或降低肾功能的患者的肾脏和心脏衰竭。涉及的保护机制包括血糖依赖性和非依赖性机制：SGLT2 抑制剂可预防高血糖和低血糖，对糖化血红蛋白（HbA1C）的净效应预计较小。诱导尿糖丢失的代谢适应包括减少脂肪量和更多酮体作为额外燃料。SGLT2 抑制剂可降低肾小球毛细血管高血压和高滤过，从而减轻滤过屏障、蛋白尿和管状重吸收的氧气需求的物理压力。这改善了皮质氧合，与较少的管状糖毒性一起，可能长期保护管状功能和肾小球滤过率。SGLT2 抑制剂可能模拟全身缺氧并刺激红细胞生成，从而改善器官氧输送。SGLT2 抑制剂是近端小管和渗透性利尿剂，可减少容量潴留和血压并保护心脏功能，部分可能是通过克服利尿剂和心房利钠肽的阻力以及抑制 Na-H 交换体和交感神经张力。
