Sotagliflozin, or LX4211, is an orally-delivered small molecule compound that is currently in development for the treatment of type 1 and type 2 diabetes mellitus.
Sotagliflozin inhibits both sodium-glucose cotransporter type 2, or SGLT2, a transporter responsible for most of the glucose reabsorption performed by the kidney, and sodium-glucose cotransporter type 1, or SGLT1, a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney. Our scientists identified mice lacking SGLT1, SGLT2 or both as having potent anti-diabetic phenotypes across multiple measures of glucose control and metabolism, and found that compounds inhibiting both targets had a favorable preclinical profile relative to compounds selective for SGLT2.
|This figure depicts a nephron, the basic functional unit of the kidney. The glucose reabsorption transporter, SGLT2, is expressed in the first segment of the proximal convoluted tubule (PCT S1) and is responsible for most of the glucose reabsorption that happens in the kidney where SGLT1 has a lesser role. Abbreviations: PCT S1 and S2, proximal convoluted tubule segments 1 and 2; PST S3, proximal straight tubule segment 3.|
|SGLT1 is the primary transporter for absorption of glucose and galactose in the gastrointestinal tract.|