Sodium-Glucose Cotransporter 2 Inhibitors: An Overview

Essie Samuel, PharmD, BCPS; Jiehyun Lee, PharmD, BCACP, CACP


US Pharmacist. 2017;42(10):42-47. 

In This Article

Mechanism of Action

More than 99% of glucose entering the kidneys and reaching the glomeruli is filtered through the nephrons. In healthy patients, the proximal tubules reabsorb glucose from the filtered urine before reaching the loop of Henle. Glycosuria occurs when a surge in plasma glucose leads to an increase in the filtered glucose reaching the kidneys, overwhelming the proximal tubules' resorptive capacity. Until recently, the mechanism of glucose reabsorption was not fully understood but was thought to be achieved by coupling sodium transport across the membrane with glucose.[3] It is now clear that the reabsorption of glucose in the proximal tubules into renal tubular epithelial cells is managed by the adenosine triphosphate–dependent protein family (SGLTs).[1] In contrast to high-affinity and low-capacity SGLT1, low-affinity and high-capacity SGLT2 is responsible for most of the glucose reabsorption in the renal tubules. In the last few years, several molecules were developed to specifically target SGLT2s for the treatment of T2DM.[3] SGLT2 inhibitors decrease the reabsorption of glucose and lower the renal threshold for glucose, consequently escalating urinary glucose excretion.[4]