(1) Background: The aim of this retrospective observational study was to evaluate the effects of sodium–glucose cotransporter-2 inhibitors (SGLT2i) therapy in patients with chronic kidney disease (CKD) who had been receiving renin–angiotensin– aldosterone system (RAAS) inhibitor (RAASi) treatment for at least one year. (2) Methods: The medical records of 73 patients with CKD, staged according to the KDIGO 2012 guidelines, were reviewed at the start of combined therapy (RAASi and SGLT2i), marked as T0, and again after six months (T1). Biochemical parameters assessed at both time points included urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), urinary albumin, urinary proteinuria, serum creatinine, and hemoglobin. (3) Results: A significant reduction in UACR (p < 0.001) and 24-hour urine albumin excretion (p = 0.050) was observed. Urine protein/24h (p = 0.074) and serum creatinine (p = 0.391) showed decreasing trends, while eGFR increased (p = 0.154), although these changes did not reach statistical significance. Regarding UACR category migration, 25% of patients improved, 74% remained stable, and only 1% worsened. (4) Conclusions: After six months of combined SGLT2i and RAASi therapy, most patients showed stable or improved renal status, suggesting a nephroprotective effect of dual therapy in CKD.
Two major trials, EMPA-REG OUTCOME trial (with Empagliflozin) and CANVAS trial (with Canagliflozin) have demonstrated the beneficial effects of SGLT2 inhibitors in patients with type 2 diabetes at risk for heart failure. SGLT2 inhibitors possess a unique pharmacological profile and have shown a significant reduction of hospitalization for heart failure in diabetic patients, immediately after treatment commencement. It seems that their effects are beneficial both in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. SGLT2 inhibitors reduce cardiovascular endpoints in patients with diabetes and high cardiovascular risk, most likely through a reduction of heart failure-related events. Empagliflozin treatment exerts beneficial effects on vascular function and central haemodynamics. Various mechanisms seem to contribute to the beneficial effects of SGLT2 inhibitors in heart failure. Taking into consideration their cardiovascular benefits and the number of ongoing trials with these drugs, there is a possibility to expand their indication to nondiabetic patients with heart failure. This review focuses on the newest insights into the beneficial effects of SGLT2 inhibitors on the cardiovascular system.
Cardiovascular-kidney-metabolic (CKM) syndrome describes the complex, bidirectional interplay among cardiovascular, renal, and metabolic dysfunctions, where impairment in one system accelerates decline in the others. This interconnected pathophysiology significantly elevates the risk and progression of heart disease, particularly heart failure, through mechanisms involving insulin resistance, systemic inflammation, neurohormonal activation, and endothelial dysfunction. In this context, therapeutic strategies targeting heart disease must address the multifaceted drivers of CKM. Recent advances highlight the need for an integrated, patient-centered approach that combines lifestyle interventions with pharmacological treatments tailored to individual cardiovascular risk. While foundational therapies such as RAAS inhibitors and statins remain essential, novel agents now offer additional prognostic and quality-of-life benefits. SGLT2 inhibitors have emerged as a cornerstone therapy, improving outcomes in heart failure with both preserved and reduced ejection fraction, independent of glycemic control. GLP-1 receptor agonists and dual GLP-1/GIP agonists like tirzepatide demonstrate cardiometabolic and renal protection, while finerenone shows promise in diabetic kidney disease and several heart failure phenotypes. These therapies not only target glycemic control but also reduce cardiovascular mortality, hospitalizations, and renal decline. Optimizing cardiovascular outcomes in CKM syndrome requires early, multifactorial therapeutic intervention, informed by evolving evidence and a deeper understanding of the heart–kidney–metabolism axis.
