Skip to main content

REVIEW article

Front. Med.

Sec. Nephrology

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1574693

Application of SGLT-2 Inhibitors in Non-Diabetic CKD: Mechanisms, Efficacy, and Safety

Provisionally accepted
Liufei Deng Liufei Deng *Bing Zhang Bing Zhang
  • Caidian District People's Hospital of Wuhan, Wuhan, China

The final, formatted version of the article will be published soon.

    Chronic kidney disease (CKD) represents a major global public health challenge, significantly impacting patients' quality of life and placing a heavy burden on healthcare systems. While diabetes and hypertension are the primary risk factors for CKD, non-diabetic CKD also constitutes a significant proportion, with its complex pathological mechanisms necessitating the development of novel therapeutic strategies. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, initially developed for diabetes management, have recently demonstrated remarkable renal and cardiovascular protective effects in patients with non-diabetic CKD. SGLT-2 inhibitors exert their effects through multiple mechanisms, including reactivating the tubulo-glomerular feedback, reducing glomerular pressure and filtration rate, decreasing proteinuria, inhibiting inflammation and fibrosis, and improving systemic metabolic parameters such as lowering blood pressure, uric acid levels, and body weight. These effects not only slow the progression of kidney function decline but also significantly reduce the risk of end-stage renal disease (ESRD) and cardiovascular events. Landmark clinical trials such as DAPA-CKD, CREDENCE, and EMPA-KIDNEY provide strong scientific evidence supporting the use of SGLT-2 inhibitors in non-diabetic CKD, demonstrating their broad clinical benefits and excellent safety profile. Despite potential adverse effects such as urinary tract infections, hypotension, and diabetic ketoacidosis, appropriate patient selection and personalized treatment strategies can effectively manage these risks. The multi-system effects of SGLT-2 inhibitors not only expand their clinical indications but also offer new hope for the comprehensive management of non-diabetic CKD patients, with significant clinical implications and broad future application potential.

    Keywords: Sodium-glucose cotransporter 2 inhibitors, safety assessment, clinical efficacy, Non-diabetic chronic kidney disease, Renal Protection Mechanisms

    Received: 11 Feb 2025; Accepted: 28 Mar 2025.

    Copyright: © 2025 Deng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Liufei Deng, Caidian District People's Hospital of Wuhan, Wuhan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

    Research integrity at Frontiers

    Man ultramarathon runner in the mountains he trains at sunset

    95% of researchers rate our articles as excellent or good

    Learn more about the work of our research integrity team to safeguard the quality of each article we publish.


    Find out more