Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease

Front Immunol. 2023 Sep 21:14:1213473. doi: 10.3389/fimmu.2023.1213473. eCollection 2023.

Abstract

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.

Keywords: SGLT-2 inhibitor; diabetic kidney disease; efficacy; renal protection mechanism; safety.

Publication types

  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / etiology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Kidney
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents

Grants and funding

This work was supported by grants from the Natural Science Foundation of Guangdong Province (2023A1515012187), Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases (2022B121203003), Discipline Construction Project of Guangdong Medical University (4SG21229G), Zhanjiang City Science and Technology Development Special Funds Competitive Allocation Project (2021A05083), Zhanjiang Science and Technology Project (2019A01027).