Renoprotective Effect of SGLT 2 Inhibitors Across Diabetic and Non-Diabetic Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a major health problem that affects individuals with and without diabetes and is associated with progressive loss of kidney function and increased cardiovascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed as glucose-lowering agents but have demonstrated substantial renoprotective effects beyond glycemic control. This literature review aimed to evaluate the renoprotective effects of SGLT2 inhibitors in diabetic and non-diabetic CKD, with particular emphasis on their mechanisms of action, effects on renal outcomes, and clinical implications. A narrative literature review was conducted using publications identified through PubMed, ScienceDirect, and Google Scholar. English-language publications published between 2016 and 2026 were considered, with randomized controlled trials, observational studies, systematic reviews, meta-analyses, and clinical guidelines prioritized. The reviewed evidence indicates that SGLT2 inhibitors protect kidney function through restoration of tubuloglomerular feedback, reduction of intraglomerular pressure and hyperfiltration, increased natriuresis, and modulation of inflammatory, oxidative, and fibrotic pathways. Major clinical trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, demonstrated reductions in albuminuria, slower decline in eGFR, and lower risk of kidney disease progression. Importantly, renal benefits were also observed in patients without diabetes, indicating that the effects of SGLT2 inhibitors are not dependent on glucose lowering. Overall, SGLT2 inhibitors represent an important therapeutic option for renoprotection across different CKD populations, although treatment should be individualized according to kidney function, underlying disease, and potential adverse effects.