The History of the Development of SGLT2 Inhibitors for the Treatment of Diabetes: From Biology to Chemistry

Diabetes mellitus (DM) is a leading cause of death, contributing to conditions like coronary artery disease, stroke, and renal disease. The sodium-glucose co-transporter 2 (SGLT2) protein plays a key role in glucose reabsorption in the kidneys, making it a target for diabetes treatment. SGLT2 inhibitors (SGLT2i) increase glucose excretion in urine by blocking reabsorption, lowering blood glucose levels in type 2 diabetes (T2D) patients. Phlorizin, first discovered in 1835, was the precursor to modern SGLT2i drugs, such as canagliflozin, dapagliflozin, and empagliflozin, approved between 2012 and 2015. These drugs show promise beyond glucose control, improving cardiovascular and kidney outcomes. Ongoing studies explore new SGLT2i medications and their potential in diabetes management.