Drugs to Treat Type 2 Diabetes

Glucose in filtered blood moves from the tubular lumen of the kidney
through tubule epithelial cells and back into the blood through sodium-
glucose linked transport (SGLT) proteins and the glucose transporter
2 (GLUT2) protein. SGLT transport proteins are Na⁺-dependent
secondary active symporter proteins that rely on the Na⁺–K⁺ ATPase
primary active transport protein to maintain a low [Na⁺] inside tubule
epithelial cells. Persons with type 2 diabetes have elevated blood glucose
levels owing to defects in the insulin signaling pathway in liver and muscle
cells. Two commonly used drugs to treat type 2 diabetes are metformin
and empagliflozin (Jardiance). Metformin stimulates the activity
of AMP-activated protein kinase (AMPK), which increases glucose
uptake by tissues. In contrast, empagliflozin inhibits the SGLT2 glucose
transport protein in kidney cells, which increases glucose excretion
in urine. The structure of empagliflozin is based on the natural product
phlorizin that was first identified in apple trees.