Sodium-glucose cotransporter 2 (SGLT2)

Class

SGLT2 inhibitor (small molecule, -gliflozin class)

Pathway

Renal proximal tubule glucose/sodium reabsorption blockade — glycosuria/natriuresis, renal and cardiovascular protection

Sodium-glucose cotransporter 2 (SGLT2) is a membrane protein located in the early segment of the kidney's proximal tubule, where it reabsorbs the majority of glucose filtered by the kidney back into the bloodstream, working together with sodium. In people with diabetes, elevated blood glucose increases the amount filtered and reabsorbed, contributing to sustained hyperglycemia. Small-molecule SGLT2 inhibitors, often called gliflozins, block this transporter, causing excess glucose to be excreted in urine (glycosuria) rather than reabsorbed, which lowers blood glucose independent of insulin secretion or action. Because sodium reabsorption is coupled to glucose transport at this site, inhibition also increases sodium and water excretion (natriuresis), producing a mild diuretic effect. This dual glycosuric and natriuretic action underlies the mechanism's relevance beyond glucose control: reduced intraglomerular pressure and volume effects are thought to confer protection against progressive kidney function decline and to reduce the workload on the heart, making this class relevant across type 2 diabetes, chronic kidney disease, and heart failure. The mechanism illustrates how a single transporter can be leveraged for metabolic, renal, and cardiovascular benefit simultaneously.