Cardiovascular And Renal Benefits of Sodium–Glucose Cotransporter 2 Inhibitors in Patients Without Diabetes: A Review of Current Evidence

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) were initially developed for the treatment of type 2 diabetes mellitus. However, recent clinical trials have demonstrated cardiovascular and renal benefits that extend to patients without diabetes, expanding their potential therapeutic role in conditions such as heart failure and chronic kidney disease.Objective: To review the available evidence regarding the role of SGLT2 inhibitors in reducing cardiovascular and renal events in patients without diabetes mellitus, with particular emphasis on major clinical trials and the mechanisms underlying these effects.Methods: A literature review will be conducted using major biomedical databases, prioritizing randomized controlled trials, systematic reviews, metaanalyses, and clinical practice guidelines. Particular attention will be given to studies evaluating dapagliflozin, empagliflozin, and other SGLT2 inhibitors in patients with heart failure or chronic kidney disease without diabetes mellitus.Results: Evidence from major randomized clinical trials indicates that SGLT2 inhibitors reduce the risk of hospitalization for heart failure and selected outcomes related to kidney disease progression, including among patients without diabetes mellitus. These benefits appear to involve hemodynamic, renal, and metabolic mechanisms that are largely independent of glucose lowering. The magnitude of benefit varies according to the clinical population, heart failure phenotype, baseline kidney function, and specific outcome evaluated.Conclusions: SGLT2 inhibitors have evolved from primarily glucose-lowering agents into an important cardiorenal therapeutic strategy for selected patients without diabetes mellitus. Current evidence supports their use in specific clinical settings involving heart failure and chronic kidney disease, although the magnitude of benefit depends on the underlying clinical context and should be interpreted according to evidence specifically derived from non diabetic populations.