SGLT2 Inhibitors beyond Diabetes: Emerging Cardiovascular, Renal and Neuroprotective Applications

Sodium-glucose cotransporter-2 (SGLT2) inhibitors first entered clinical use as glucose-lowering drugs for type 2 diabetes mellitus. Their therapeutic scope has since widened considerably, driven by evidence of cardiovascular and renal benefits that go beyond glycaemic control. These agents promote urinary excretion of glucose and sodium, and they produce broad systemic effects involving renal haemodynamics, plasma volume, myocardial metabolism, vascular function, inflammation, and oxidative stress. Clinical trials have confirmed meaningful benefits in heart failure and chronic kidney disease, including in patients without diabetes. Dapagliflozin and empagliflozin have reduced hospitalisations for heart failure and cardiovascular events across different heart-failure phenotypes, while canagliflozin, dapagliflozin, and empagliflozin have shown protection against the progression of chronic kidney disease. Interest has also grown in possible neurological effects. Experimental studies and observational clinical data suggest that SGLT2 inhibitors may influence neuroinflammation, oxidative stress, mitochondrial dysfunction, cerebral vascular injury, and cognitive decline. However, the evidence for neuroprotection is far less mature than the cardiovascular and renal data, and causality has not been established. This review summarizes the pharmacological basis of the extra-glycaemic effects of SGLT2 inhibitors, evaluates their established cardiovascular and renal applications, examines emerging neuroprotective evidence, discusses safety considerations, and identifies future research priorities. The growing body of evidence indicates that SGLT2 inhibitors have moved from conventional antihyperglycaemic agents to important components of modern cardiorenal pharmacotherapy, while their potential role in neurological disease remains a key area for further study.