Indications
Sotagliflozin is prescribed in the United States to decrease the risk of cardiovascular death and heart failure in adult patients. This includes those with heart failure, type 2 diabetes mellitus, chronic kidney disease, and other associated cardiovascular risk factors.
Pharmacodynamics
Sotagliflozin functions pharmacologically by decelerating glucose absorption within the gastrointestinal tract and enhancing glucose excretion through the urine. It is administered orally once daily prior to the first meal. The drug belongs to the class of SGLT2 inhibitors, which carry a risk of inducing diabetic ketoacidosis (DKA). Patients, particularly those predisposed to DKA, should be educated on the symptoms and monitoring protocols for ketoacidosis, as well as the necessary steps to take should it be suspected. Additionally, the use of SGLT2 inhibitors, sotagliflozin included, elevates the risk of genital infections due to increased urinary glucose levels, providing a conducive environment for infectious agents.
Absorption
Post-administration of a single dose of sotagliflozin, the time to reach maximum plasma concentration (Tmax) ranges from 1.25 to 3 hours. With consecutive dosing, this range extends from 2.5 to 4 hours. Sotagliflozin has an estimated oral bioavailability of 71%.
Metabolism
Sotagliflozin undergoes metabolism primarily to its major inactive metabolite, 3-O-glucuronide (M19), which accounts for approximately 94% of the radioactivity detected in plasma following administration of a radiolabeled dose. The activity of this metabolite at SGLT1 and SGLT2 is significantly lower, over 275 times less, than that of sotagliflozin itself. Metabolism predominantly occurs through glucuronidation via UGT1A9, with additional minor pathways involving UGT1A1, UGT2B7, and oxidation via CYP3A4.
Mechanism of Action
Sotagliflozin operates as a dual inhibitor, targeting both sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 primarily facilitates glucose absorption within the gastrointestinal tract, whereas SGLT2 predominantly governs the reabsorption of glucose in the renal glomerulus. By inhibiting SGLT1, sotagliflozin delays glucose absorption and mitigates postprandial hyperglycemia. Concurrently, the inhibition of SGLT2 decreases renal glucose reabsorption, leading to enhanced urinary glucose excretion.
