Cureus. 2026 Sep 5;18(9):e115840. doi: 10.7759/cureus.115840. eCollection 2026 Sep.
ABSTRACT
Chronic kidney disease (CKD) is a major global health concern characterized by progressive loss of kidney function and an increased risk of cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, initially developed as antihyperglycemic agents for the treatment of type 2 diabetes mellitus (T2DM), have subsequently demonstrated substantial renoprotective effects that extend beyond glycemic control. This systematic review aimed to evaluate current evidence regarding the effects of SGLT-2 inhibitors on CKD progression in adults with and without diabetes. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Google Scholar from database inception through October 2025. Eligible studies included randomized controlled trials (RCTs), systematic reviews and meta-analyses, and prospective or retrospective observational cohort studies evaluating kidney outcomes, including CKD progression, changes in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, and progression to end-stage kidney disease (ESKD). The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Thirty-two studies met the inclusion criteria, comprising 13 RCTs, eight systematic reviews and meta-analyses, and 11 observational cohort studies. Across randomized trials, SGLT-2 inhibitors consistently reduced CKD progression and major adverse kidney outcomes and slowed the decline in kidney function. Dedicated kidney outcome trials demonstrated substantial reductions in adverse kidney outcomes, while meta-analytic evidence confirmed preservation of kidney function across diverse CKD populations, including individuals without diabetes. Real-world observational studies further supported these findings, demonstrating slower eGFR decline and favorable kidney outcomes in routine clinical practice. SGLT-2 inhibitors were generally well tolerated, and meta-analytic evidence demonstrated a reduced risk of acute kidney injury among patients with CKD. Collectively, the available evidence indicates that SGLT-2 inhibitors substantially slow CKD progression and reduce adverse kidney outcomes across diverse CKD populations, including patients with and without diabetes. Their consistent efficacy and favorable safety profile support their role as cornerstone nephroprotective agents in contemporary CKD management. Further research is warranted to clarify their long-term efficacy and safety in underrepresented populations, particularly patients with advanced CKD and non-albuminuric disease.
PMID:42840550 | PMC:PMC13639324 | DOI:10.7759/cureus.115840