Sodium-glucose cotransporters 1 and 2 (SGLT1/SGLT2)

Sodium-glucose cotransporter 1 and 2 (SGLT1, SGLT2) are membrane transport proteins that mediate the active reuptake of glucose in the intestines (SGLT1) and kidneys (SGLT2), respectively, via sodium-coupled co-transport. SGLT2 is responsible for ~90% of renal glucose reabsorption, while SGLT1 manages absorption of glucose from dietary sources in the gut and the remaining renal glucose reabsorption. Inhibition of these transporters promotes glucose and sodium excretion, supporting glycemic control, cardiovascular risk reduction, and renal protection in patients with diabetes and related conditions. Several SGLT2 inhibitors are clinically approved, and dual SGLT1/SGLT2 inhibition (sotagliflozin) is a new therapeutic approach with distinct pharmacodynamic properties and risks.

Other names

SGLT family membersSLC5A1SLC5A2Sodium-glucose transport protein 1Sodium-glucose transport protein 2

Inhibition of SGLT2 decreases renal glucose reabsorption, leading to increased urinary glucose excretion and lower blood glucose. Inhibition of SGLT1 (alone or combined) reduces intestinal absorption of dietary glucose and blunts postprandial glucose spikes. Dual SGLT1/SGLT2 inhibition increases both urinary and fecal excretion of glucose and sodium.