Lapuerta Pablo, Zambrowicz Brian, Strumph Paul, Sands Arthur
Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA
Lexicon Pharmaceuticals, Inc., Princeton, NJ, USA.
Diab Vasc Dis Res. 2015 Mar;12(2):101-10. doi: 10.1177/1479164114563304.
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.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是治疗糖尿病的一类重要的新兴药物。SGLT2抑制剂的研发围绕着对SGLT2蛋白相对于SGLT1蛋白具有高选择性的需求展开。最近，对小鼠的遗传学和药理学研究表明，抑制胃肠道中的SGLT1也可能是治疗糖尿病的一个合适的治疗靶点。在单个分子中同时抑制SGLT1和SGLT2将提供互补的非胰岛素依赖机制来治疗糖尿病。因此，索格列净（LX4211）已被开发为SGLT1和SGLT2的双重抑制剂。SGLT1和SGLT2双重抑制剂的独特临床特征包括餐后血糖大幅降低、胰高血糖素样肽1升高以及适度的尿糖排泄。这些特征可能对索格列净用于治疗1型和2型糖尿病具有临床意义。
