Empagliflozin

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

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

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Oral hypoglycaemic agents

This chemical does not meet GHS hazard criteria for 22.2% (2 of 9) of reports.

Warning

H302 (33.3%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P263, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 9 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The most commonly reported side effects were urinary tract infections, genital mycotic infections, and dyslipidemia. Due to its diuretic properties related to volume depletion, there were also reports of dehydration, hypotension, hypovolemia, and syncope. The FDA issued a warning for Fournier gangrene, a type of necrotizing fasciitis of the perineum. There were twelve reported cases, and all twelve were hospitalized, requiring surgical debridement. If suspected, stop the drug and have the patient report to the ED promptly for a surgical evaluation.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Empagliflozin

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

A10BK03

Empagliflozin lowers blood glucose levels by preventing glucose reabsorption in the kidneys, thereby increasing the amount of glucose excreted in the urine. It has a relatively long duration of action requiring only once-daily dosing. Patients should be monitored closely for signs and symptoms of ketoacidosis regardless of blood glucose level as empagliflozin may precipitate diabetic ketoacidosis in the absence of hyperglycemia. As its mechanism of action is contingent on the renal excretion of glucose, empagliflozin may be held in cases of acute kidney injury and/or discontinued in patients who develop chronic renal disease. The overexcretion of glucose creates a sugar-rich urogenital environment which increases the risk of urogenital infections in both male and female patients - monitor closely for signs and symptoms of developing infection.

The vast majority of glucose filtered through the glomerulus is reabsorbed within the proximal tubule, primarily via SGLT2 (sodium-glucose linked co-transporter-2) which is responsible for ~90% of the total glucose reabsorption within the kidneys. Na⁺/K⁺-ATPase on the basolateral membrane of proximal tubular cells utilize ATP to actively pump Na+ ions into the interstitium surrounding the tubule, establishing a Na⁺ gradient within the tubular cell. SGLT2 on the apical membrane of these cells then utilize this gradient to facilitate secondary active co-transport of both Na+ and glucose out of the filtrate, thereby reabsorbing glucose back into the blood – inhibiting this co-transport, then, allows for a marked increase in glucosuria and decrease in blood glucose levels. Empagliflozin is a potent inhibitor of renal SGLT2 transporters located in the proximal tubules of the kidneys and works to lower blood glucose levels via an increase in glucosuria. Empagliflozin also appears to exert cardiovascular benefits - specifically in the prevention of heart failure - independent of its blood glucose-lowering effects, though the exact mechanism of this benefit is not precisely understood. Several theories have been posited, including the potential inhibition of Na⁺/H⁺ exchanger (NHE) 1 in the myocardium and NHE3 in the proximal tubule, reduction of pre-load via diuretic/natriuretic effects and reduction of blood pressure, prevention of cardiac fibrosis via suppression of pro-fibrotic markers, and reduction of pro-inflammatory adipokines.