G Ital Nefrol. 2026 Jun 30;43(3):2026-vol3. doi: 10.69097/43-03-2026-09.
ABSTRACT
Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2i), initially developed as hypoglycemic agents, have revolutionized the management of cardiorenal diseases due to potent organ-protective effects. Evidence from large clinical trials (DAPA-CKD, EMPA-KIDNEY, DAPA-HF, EMPEROR-Preserved) has established that their renal and cardiac benefits manifest independently of the presence of Type 2 Diabetes Mellitus (T2DM). Renally, nephroprotection mainly stems from the restoration of tubulo-glomerular feedback, which reduces hyperfiltration and intraglomerular pressure, thereby mitigating structural damage in non-diabetic Chronic Kidney Disease (CKD). Cardiologically, SGLT2i improve myocardial metabolism and reduce congestion, demonstrating efficacy in both Heart Failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). This review synthesizes the pleiotropic mechanisms of action and the clinical evidence that extends the use of SGLT2i across the entire spectrum of CKD (eGFR ≥ 20 mL/min/1.73 m2) and Heart Failure offering practical considerations for clinicians regarding dosing and the management of adverse events, such as the initial eGFR dip and the prevention of euglycemic ketoacidosis.
PMID:42423061 | DOI:10.69097/43-03-2026-09