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Pharmaceutical chemistry of sodium glucose co-transporter 2 inhibitors (SGLT2-I)

Allison Butts, Aaron Cook

According to the World Health Organization, Diabetes Mellitus (DM) is one of the top causes of mortality in 2019. It is also regarded as a key contributor to other illnesses such as heart attack, stroke, kidney failure, blindness, and lower limb amputation. A protein called Sodium Glucose Co-Transporter 2 (SGLT2) reabsorbs about 90% of the glucose present in plasma glucose. For the treatment and management of diabetes, SGLT2 is a known target. SGLT2 inhibitors (SGLT2-I) are now available on the market to control blood glucose levels in people with diabetes. The human body contains six SGLT proteins, each of which has a different predilection for binding sugar. The SGLT2 enzyme, which is mostly found in the gut and early proximal tubule of the nephron and promotes glucose absorption by around 90%, is the target of the therapeutic strategy. As SGLT2 expression and tubular glucose load rise in the diabetic state, glucose reabsorption results in hyperglycemia. SGLT2-I works by preventing the reabsorption of glucose into the renal tubule and increasing the excretion of glucose through the urine. The identification and creation of selective SGLT2-I hold considerable promise for the management and treatment of diabetes mellitus.

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