Cariou Bertrand, Charbonnel Bernard
a Clinique d'Endocrinologie , l'institut du thorax , CHU de Nantes, Nantes F-44000 , France.
b l'institut du thorax , Inserm, UMR1087, Nantes F-44000 , France.
Expert Opin Investig Drugs. 2015;24(12):1647-56. doi: 10.1517/13543784.2015.1100361. Epub 2015 Nov 7.
SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM).
Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. Original publications in English were selected as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database.
By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secretion, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. While sotagliflozin was first assessed in T2DM, it is now in phase 3 development as an adjuvant treatment in patients with T1DM after positive results from a pilot study.
SGLT1是负责肠道中葡萄糖和半乳糖吸收的主要转运蛋白,而SGLT2和SGLT1均参与肾脏对葡萄糖的重吸收。SGLT2抑制剂是一类新型口服抗糖尿病药物,通过增加尿糖排泄(UGE)发挥作用。它们具有降低低血糖风险、减轻体重和血压以及在2型糖尿病(T2DM)各阶段均有效的优点。
在此,作者特别关注索格列净(LX4211),这是一流的双SGLT1/SGLT2抑制剂。以英文原始出版物作为本综述的基础。使用Clinicaltrial.gov数据库识别临床试验。
通过与SGLT1抑制相关的对肠道葡萄糖吸收的潜在额外作用机制,索格列净与SGLT2抑制剂不同,它可减少餐后血糖波动和胰岛素分泌,并增加GLP-1分泌。尽管索格列净对UGE的作用比选择性SGLT2抑制剂弱,但在降低糖化血红蛋白(HbA1C)方面与SGLT2抑制剂一样有效,在短期研究中具有相似的安全性。虽然索格列净最初是在T2DM中进行评估的,但在一项初步研究取得阳性结果后,它目前正处于作为1型糖尿病(T1DM)患者辅助治疗的3期开发阶段。