title: Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor.
abstract: The sodium-dependent glucose transporter 2 (SGLT2) inhibitors are an important emerging class for the treatment of diabetes. Development of SGLT2 inhibitors has been oriented around a desire for high selectivity for the SGLT2 protein relative to the SGLT1 protein. More recently, genetic and pharmacology research in mice has indicated that gastrointestinal SGLT1 inhibition may also be an appropriate therapeutic target to treat diabetes. Combining SGLT1 and SGLT2 inhibition in a single molecule would provide complementary insulin-independent mechanisms to treat diabetes. Therefore, sotagliflozin (LX4211) has been developed as a dual inhibitor of SGLT1 and SGLT2. The differentiating clinical features of dual inhibitor of SGLT1 and SGLT2 include a large postprandial glucose reduction, elevation of glucagon-like peptide 1 and modest urinary glucose excretion. These features may have clinical implications for the use of sotagliflozin in the treatment of both type 1 and type 2 diabetes.
authors.affiliation: Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA plapuerta@lxrx.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuerta
authors.affiliation: Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zambrowicz
authors.affiliation: Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Strumph
authors.affiliation: Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA Baylor College of Medicine, Houston, TX, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Sands
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D055808:Drug Discovery; D006027:Glycosides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D065667:Renal Elimination / Q000187:drug effects; D065608:Renal Reabsorption / Q000187:drug effects; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006027:Glycosides; D007004:Hypoglycemic Agents; C495674:SLC5A1 protein, human; C089180:SLC5A2 protein, human; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C575681:(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
keywords: LX4211; diabetes mellitus; diabetes mellitus type 2; glucagon-like peptide 1; sodium-glucose transporter 1; sodium-glucose transporter 2; sotagliflozin; type 1