Sotagliflozin

Breast Feeding; Lactation; Milk, Human; Hypoglycemic Agents; Sodium-Glucose Cotransporter 2 Inhibitors; SGLT2 Inhibitors

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 50% (2 of 4) of reports.

Warning

H302 (25%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 4 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In two large pre-registration, placebo-controlled cardiovascular outcome trials that enrolled more than 11,000 patients, serum aminotransferase elevations were no more frequent with sotagliflozin than with placebo. Rates of ALT elevations above 3 times the upper limit of normal (ULN) were similar between treatment groups (2.0% vs 2.1% in the heart failure trial; 0.9% vs 0.9% in the diabetes and kidney disease trial), and mean aminotransferase levels did not change with treatment. Potential cases of drug-induced liver injury, adjudicated by a committee blinded to the treatment group, occurred at similarly low rates in the sotagliflozin and placebo patients [1.8% vs 2.3% and 0.7% vs 0.6%]. A single sotagliflozin-treated patient met laboratory criteria for clinically apparent liver injury with jaundice, but the event occurred months after stopping the drug and was judged to be due to biliary obstruction from gallstones. The product label does not list liver injury as an adverse reaction. Since its approval, there have been no published reports of clinically apparent liver injury attributed to sotagliflozin, but clinical experience with the drug has been limited. As with other agents in the SGLT2 inhibitor class, sotagliflozin appears to be an unlikely cause of liver injury.

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

Sotagliflozin exerts its pharmacologic effects by slowing glucose absorption in the gastrointestinal tract and increasing the excretion of glucose in the urine. It is administered by mouth once daily before the first meal of the day. The use of SGLT2 inhibitors, including sotagliflozin, can cause diabetic ketoacidosis (DKA). Patients, especially those with a higher baseline risk of DKA, should be instructed on how and when to monitor for ketoacidosis and what actions to take when DKA is suspected. SGLT2 inhibitors, including sotagliflozin, also increase the risk of genital infections. This is due to the increase in urinary glucose excretion, which provides a relatively glucose-rich environment in which infectious agents may establish themselves.

Sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2) are integral in the transport of glucose in the body. SGLT1 is the major transporter for glucose absorption in the gastrointestinal tract, while SGLT2 is the predominant transporter responsible for reabsorption of glucose in the glomerulus. Sotagliflozin is a dual inhibitor of both SGLT1 and SGLT2. Inhibition of SGLT1 results in a delay in glucose absorption and a blunting of postprandial hyperglycemia, while inhibition of SGLT2 reduces renal reabsorption of filtered glucose, thereby increasing urinary glucose excretion.

The major metabolite of sotagliflozin is a 3-O-glucuronide (M19), which comprised ~94% of of the radioactivity in plasma following the oral administration of a radiolabeled dose of sotagliflozin. The M19 metabolite is effectively inactive, with >275-fold less activity at SGLT1 and SGLT2 compared to the parent drug. The primary route of metabolism is via glucuronidation by UGT1A9 (and both UGT1A1 and UGT2B7, to a lesser extent) as well as oxidation via CYP3A4.