Inhibitors of sodium-glucose co-transporters in the treatment of diabetic nephropathy and chronic kidney disease: A narrative review

Abstract

Background: Chronic kidney disease (CKD) is a global health problem, ranking as the 12 th leading cause of disability and the 9 th leading cause of death worldwide, affecting over 14% of adults. Among the causes is diabetic nephropathy (DN), a common microvascular complication of diabetes characterised by albuminuria and reduced glomerular filtration rate, often progressing to end-stage renal disease. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, originally developed as antidiabetic agents, have shown nephroprotective effects beyond glucose control, including podocyte preservation, normalisation of intrarenal pressure, reduced uric acid levels, improved mitochondrial function, and anti-inflammatory actions. Aim: We evaluate preclinical and clinical research and assess the role and place of SGLT inhibitors in treating and slowing the progression of diabetic nephropathy and other forms of chronic kidney disease. Materials and methods: Data on SGLT-2 inhibitors were included and analysed, as well as published data from basic research and the landmark kidney and cardiovascular outcome trials. Published meta-analyses were also synthesised. Results: Extensive preclinical and clinical studies, including large studies such as CREDENCE, EMPA-Kidney, and DAPA-CKD, have confirmed that SGLT-2 inhibitors slow CKD progression and reduce cardiovascular risk in patients with and without diabetes. These drugs improve endothelial function, modulate the renin-angiotensin-aldosterone system, and attenuate sympathetic nervous system overactivity, providing cardiovascular and renal protection. Meta-analyses have confirmed their benefit in reducing major adverse cardiovascular events, hospitalisations for heart failure, and all-cause mortality in various patient populations. Network analyses have highlighted differences among SGLT-2 inhibitors, with empagliflozin showing superior mortality benefits. Conclusions: SGLT-2 inhibitors are a fundamental therapy for cardiorenal syndrome and diabetic nephropathy (DN), but further studies are needed to define their molecular mechanisms and optimise patient-specific treatment strategies. Accumulating real-world data would improve their clinical value in treating renal and cardiovascular diseases.