SGLT2 Inhibitors in Heart Failure with Coexisting Chronic Kidney Disease

Background. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have evolved from their origins as antihyperglycemic agents to become a cornerstone of cardiorenal therapy. The high prevalence of coexisting heart failure (HF) and chronic kidney disease (CKD) creates a complex clinical syndrome where traditional glucose-centric management is insufficient. Aim. To provide an exhaustive narrative scientific review of the clinical, molecular, and guideline-driven evidence for SGLT2 inhibitors in patients with concurrent heart failure and chronic kidney disease, emphasizing outcomes that transcend glycemic control. Material and methods. A narrative literature review was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library for articles published between January 2015 and January 2026. Keywords included "SGLT2 inhibitors", "heart failure", "chronic kidney disease", "eGFR", "albuminuria", and "cardiorenal syndrome". Results. Large-scale randomized controlled trials (DAPA-HF, EMPEROR-Reduced, DAPA-CKD, and EMPA-KIDNEY) and recent meta-analyses like SMART-C (2025) demonstrate that SGLT2 inhibitors reduce cardiovascular death and heart failure hospitalizations by approximately 25%, while slowing renal progression by 30-40% across various eGFR and albuminuria strata. These benefits are mediated through the restoration of tubuloglomerular feedback, metabolic switching toward oxygen-efficient ketone bodies, and direct anti-inflammatory pathways. Conclusions. SGLT2 inhibitors are foundational therapies for the cardiorenal axis. Their use is now recommended down to an eGFR of 20 mL/min/1.73 m², with benefits extending into advanced CKD stages. Clinicians must integrate these agents early in the disease course to maximize organ preservation and survival.