Sotagliflozin is an orally-delivered small molecule compound for which we have filed a new drug application (NDA), currently pending before the FDA, for the treatment of heart failure and that we are separately developing in type 1 diabetes. Our scientists identified the targets of sotagliflozin, sodium-glucose cotransporter type 1 (SGLT1) and sodium-glucose cotransporter type 2 (SGLT2) in our target discovery efforts based on their discovery that mice lacking SGLT1, SGLT2 or both exhibited potent anti-diabetic phenotypes across multiple measures of glucose control and metabolism in preclinical models. Preclinical studies of sotagliflozin demonstrated that compounds inhibiting both targets had a favorable preclinical profile relative to compounds selective for SGLT2. SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose and sodium reabsorption by the kidney.
- SGLT1 is the primary transporter for glucose and galactose in the gastrointestinal (GI) tract
- Inhibiting SGLT1 in the GI tract reduces post-prandial glucose and elevates GI hormones such as GLP-1 and PYY that have been associated with metabolic benefits
- Mechanism is independent of insulin and is not affected by declining renal function
- SGLT2 reabsorbs 90% of filtered glucose in the kidney
- Inhibiting SGLT2 in the kidney increases glucose excretion in the urine, resulting in reduced blood glucose
- Mechanism is independent of insulin but diminishes in effect with declining renal function