Sodium-glucose cotransporter 2 inhibitors in chronic kidney disease: A review of current evidence and clinical implications

Abstract

Background

Chronic kidney disease (CKD) is a progressive condition affecting millions worldwide, leading to substantial morbidity, mortality, and healthcare burden. While traditional treatments such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been the cornerstone of CKD management, newer therapeutic approaches are needed to slow disease progression and improve outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed as antihyperglycemic agents, have demonstrated significant renoprotective and cardioprotective effects beyond glucose control.

Objective

This review aims to evaluate the current evidence on the efficacy, safety, and clinical implications of SGLT2 inhibitors in CKD, highlighting their mechanisms of action, benefits, limitations, and future research directions.

Methods

A comprehensive literature search was conducted in PubMed, Google Scholar, and Medline using keywords related to SGLT2 inhibitors, CKD, and renal outcomes with no time limit. Studies included randomized controlled trials, cohort studies, and case-control studies examining the effects of SGLT2 inhibitors on renal and cardiovascular outcomes in CKD patients. The risk of bias was assessed using standard tools such as the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool.

Results

Clinical trials have demonstrated that SGLT2 inhibitors, including empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin, significantly reduce CKD progression, lower albuminuria, and decrease the risk of cardiovascular events and all-cause mortality. These effects are observed in both diabetic and non-diabetic populations. Additionally, SGLT2 inhibitors exhibit renoprotective mechanisms such as reducing glomerular hyperfiltration, modulating tubuloglomerular feedback, and exerting anti-inflammatory and antifibrotic properties. However, potential adverse effects, including an initial decline in estimated glomerular filtration rate (eGFR), an increased risk of euglycemic diabetic ketoacidosis, and urinary tract infections, necessitate careful patient selection and monitoring. Emerging studies also explore the role of machine learning in optimizing SGLT2 inhibitor use for personalized treatment approaches.

Conclusion

SGLT2 inhibitors have emerged as a transformative addition to CKD management, offering substantial renal and cardiovascular benefits. Despite safety concerns, their advantages outweigh the risks, warranting broader clinical implementation. Future research should focus on refining patient selection, optimizing treatment combinations, and leveraging data science to enhance therapeutic outcomes in CKD patients.