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

Background: : Sodium–glucose cotransporter 2 (SGLT2) inhibitors were initially developed to improve glycemic control in type 2 diabetes. Large cardiovascular and kidney outcome trials subsequently demonstrated benefits that extend beyond glucose lowering, including among participants without diabetes. This evidence has changed the treatment of heart failure and chronic kidney disease (CKD), but the magnitude and clinical meaning of benefit vary by disease phenotype and outcome. Objective: To summarize the clinical evidence for cardiovascular and renal effects of SGLT2 inhibitors in adults without diabetes, emphasizing heart failure across the ejection-fraction spectrum, CKD progression, potential mechanisms, safety, and implications for practice. Methods: : This narrative review synthesizes landmark randomized controlled trials, prespecified and post hoc analyses by glycemic status, and major clinical practice guidelines. The discussion prioritizes trials that enrolled participants without diabetes or reported treatment effects by diabetes status. This document is a narrative synthesis rather than a completed systematic review; no exhaustive database search, duplicate screening, formal risk-of-bias assessment, or PRISMA study-flow count is claimed. Results: : In heart failure with reduced ejection fraction, DAPA-HF demonstrated that dapagliflozin reduced worsening heart failure or cardiovascular death, with consistent effects in participants with and without diabetes. EMPEROR-Preserved and DELIVER extended evidence to patients with mildly reduced or preserved ejection fraction, with benefits driven predominantly by fewer worsening-heart-failure events. In CKD, DAPA-CKD and EMPA-KIDNEY showed slower kidney disease progression in populations that included people without diabetes, with broadly consistent relative effects across glycemic subgroups. Proposed mechanisms include altered renal hemodynamics, natriuresis, changes in tubuloglomerular feedback, and broader cardiorenal effects that are not dependent on lowering blood glucose. Important risks include genital mycotic infection, volume depletion in susceptible patients, and rare ketoacidosis, including euglycemic presentations. Conclusions: : Evidence supports the use of selected SGLT2 inhibitors for eligible patients with heart failure or CKD regardless of diabetes status. Treatment decisions should be based on the relevant indication, kidney function, volume status, concomitant therapy, contraindications, and current local prescribing information. Benefits should not be generalized to every cardiovascular outcome or every patient subgroup.