Comparison of SGLT1, SGLT2, and Dual Inhibitor Biological Activity in Treating Type 2 Diabetes Mellitus

Diabetes Mellitus Type 2 (T2D) is an emerging health burden in the US and worldwide, impacting ≈15% of Americans. Current front-line therapeutics for T2D patients include sulfonylureas that act to reduce A1C and fasting blood glucose levels, or Metformin that antagonizes the action of glucagon to reduce hepatic glucose production. Next-generation glucomodulatory therapeutics target members of the high-affinity glucose transporter sodium-glucose-linked-transporter (SGLT) family. SGLT1 is primarily expressed in intestinal epithelium, whose inhibition reduces dietary glucose uptake, whilst SGLT2 is highly expressed in kidney regulating glucose reabsorption. A number of SGLT2 inhibitors are FDA approved whilst SGLT1 and dual SGLT1 & 2 inhibitor are currently in clinical trials. Here, SGLT2, SGLT1, and dual inhibitors’ biochemical mechanism and physiological effects are discussed and compared.