The Impact of SGLT2 Inhibitors on The Progression of Chronic Kidney Disease

Abstract

Introduction: Chronic Kidney Disease (CKD) is a progressive condition leading to significant morbidity and mortality. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, originally for type 2 diabetes, have shown significant benefits in slowing CKD progression, regardless of diabetes status. This review summarizes the mechanisms and clinical impact of SGLT2 inhibitors on CKD patients.

Methods: This is a narrative review of existing literature. Information was synthesized from academic papers, focusing on CKD pathophysiology and the role, mechanisms, and clinical evidence for SGLT2 inhibitors in providing renal protection

Results: SGLT2 inhibitors protect the kidneys through multiple pathways. They reduce glomerular hyperfiltration by promoting natriuresis and activating tubuloglomerular feedback. They also exhibit anti-inflammatory, anti-oxidative, and anti-fibrotic effects, partly by downregulating the TGF-β pathway. These agents induce a metabolic shift towards ketogenesis, improving mitochondrial energy efficiency. Additional benefits include stimulating erythropoietin (EPO) production to improve tissue oxygenation, modulating autophagy, inhibiting the sympathetic nervous system, improving endothelial function, and reducing serum uric acid. Landmark trials like DAPA-CKD, EMPA-KIDNEY, and CREDENCE have consistently shown that SGLT2 inhibitors significantly reduce GFR decline and progression to end-stage renal disease..

Conclusions: SGLT2 inhibitors represent a fundamental advance in CKD management. Their multifaceted mechanisms offer robust renoprotection beyond glycemic control, supporting their use as a foundational therapy to slow disease progression and lower cardiovascular risk.