Sotagliflozin (LX-4211) is a potent dual SGLT2/1 inhibitor and used as antidiabetic agents.LX4211 enhanced urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption; markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA(1c); and significantly lowered serum triglycerides. LX4211 also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In clinical, patients with T2DM, LX4211 (300 mg) significantly increased glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption [1]. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone [2].
体外研究
Sotagliflozin (LX-4211) is a potent dual SGLT2/1 inhibitor and used as antidiabetic agents.LX4211 enhanced urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption; markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA(1c); and significantly lowered serum triglycerides. LX4211 also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In clinical, patients with T2DM, LX4211 (300 mg) significantly increased glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption [1].
LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone [2].
Sotagliflozin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C2C12 skeletal muscle cells
5-20 µM
24 hours
Sotagliflozin pretreatment significantly enhanced the expression levels of angiogenic factors HIF-1α, VEGF-A, and PDGF-BB in HG-treated C2C12 cells under hypoxia, as well as the secreted amounts of VEGF-A and PDGF-BB in the medium.
Acta Pharmacol Sin. 2022 Oct;43(10):2636-2650.
Sotagliflozin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Diabetic hindlimb ischemia (HLI) model
Intramuscular injection
10 mg/kg
Once every 3 days for 3 weeks
Intramuscular injection of sotagliflozin effectively promoted the formation of functional blood vessels, leading to significant recovery of blood perfusion in diabetic HLI mice.
Acta Pharmacol Sin. 2022 Oct;43(10):2636-2650.
C57BL/6J mice
Cardiac pressure overload model
Oral gavage
10 mg/kg
Once daily for 7 weeks
Sotagliflozin attenuated TAC-induced cardiac hypertrophy and fibrosis in normal diet mice but did not show cardioprotective effects in high-fat diet mice.
Front Physiol. 2021 Sep 21;12:738594
Rabbits
CF rabbit model
Oral
15 mg/kg
Once daily, until the experiment endpoint (150 days or older)
To evaluate the systemic effects of Sotagliflozin on lifespan, appetite, body weight, liver function, etc., in CF rabbits. Results showed that Sotagliflozin significantly extended the lifespan of CF rabbits, improved appetite and body weight, and alleviated liver fibrosis and NASH-like phenotypes.
JCI Insight. 2024 Feb 15;9(6):e165826
Rats
ZSF-1 obese rats (a metabolic syndrome-related HFpEF model)
Oral feeding
30 mg/kg/d
Once daily for 6 weeks
Sotagliflozin ameliorated LA enlargement in HFpEF rats and reduced the magnitude of spontaneous Ca2+ release events in LA cardiomyocytes.
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