Role of SGLT Inhibitors in Treatment of Type 2 DiaRole of SGLT Inhibitors in Treatment of Type 2 Diabetes and Obesity
Glucose (sugar) is transported across the cells in the human body by a family of energy-dependent Sodium-Dependent Glucose Transporters (SGLTs). The kidneys filter approximately 180 gm. of glucose per day from the blood which is then mostly reabsorbed back into the blood. SGLT Specific Inhibitors inhibit the glucose reabsorption process, such that excess glucose is excreted in the urine, rather than reabsorbed into the bloodstream. That is to say, they have a hypoglycemic effect.
Chemically, most of the known SGLT inhibitors are derived from the prototype phlorizin and structurally are glycosides. Isolated from nature, phlorizin has been identified as having a hypoglycemic effect by inhibiting excessive glucose re-absorption in the kidney and accelerating glucose excretion. However, when administered orally phloridzin derivatives are hydrolyzed by the action of the glycosidase present in the small intestine, thus resulting in low absorption efficiency. Currently, there are no “stable mimetics” for SGLT glycosides which preserve their electronic architecture and behaviour, but eliminate or decrease hydrolization. In the stabilized SGLT inhibitors already developed, when the stabilization is efficient, it leads to drastic changes in the architecture of the sugar and then to its selectivity. When the sugar’s architecture is largely unchanged there is only a slight improvement in the efficacy.