In this article, we will introduce a potent and orally available SGLT2/1 Inhibitor, Sotagliflozin (LX-4211). It exhibits IC₅₀ values of 0.0018 µΜ and 0.036 µM for SGLT-2 and SGLT-1, respectively. Sotagliflozin’s effectiveness in inhibiting SGLT-2 is similar to that of the selective SGLT-2 inhibitors Dapagliflozin and Canagliflozin. However, it is > 10-fold more potent than Dapagliflozin/Canagliflozin in inhibiting SGLT-1.

On date  2023 May 26, FDA approved a new drug application for Sotagliflozin (Inpefa). This is the first dual SGLT1 and SGLT2 inhibitor for the treatment of heart failure (HF), including HF with preserved ejection fraction and HF with reduced ejection fraction. Furthermore, Sotagliflozin joins Dapagliflozin and Empagliflozin as the third FDA-approved drug boasting SGLT2 inhibition.

Additionally, Sotagliflozin (LX-4211) is an SGLT2/1 Inhibitor for type 2 diabetes research.

Sotagliflozin (LX-4211) treatment improves glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) in type 2 diabetes mellitus (T2DM) in clinical.  In the mouse model, Sotagliflozin (LX-4211) enhances urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption. And it markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA(1c). Additionally, it significantly lowered serum triglycerides. Sotagliflozin (LX-4211) also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels.

In a single-dose study in 12 patients with T2DM, LX4211 (300 mg) significantly increases glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption. LX4211-treated mice and SGLT1-/- mice also have 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.

In conclusion, Sotagliflozin (LX-4211) is a potent dual SGLT2/1 inhibitor and a potent antidiabetic agent.

Reference:

[1] Zambrowicz B, et al. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.

[2] Powell DR, et al. J Pharmacol Exp Ther. 2013 May;345(2):250-9.