Empagliflozin

Absorption

Following oral administration, peak plasma concentrations are reached in approximately 1.5 hours (Tmax). At steady-state, plasma AUC and Cmax were 1870 nmol·h/L and 259 nmol/L, respectively, following therapy with empagliflozin 10mg daily and 4740 nmol·h/L and 687 nmol/L, respectively, following therapy with empagliflozin 25mg daily. Administration with food does not significantly affect the absorption of empagliflozin.

Toxicity

Experience with empagliflozin overdose is limited - employ standard symptomatic and supportive measures, as well as gastric decontamination when appropriate. The use of hemodialysis in empagliflozin overdose has not been studied but is unlikely to be of benefit given the drug's relatively high protein-binding.

Description

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved by the FDA for the treatment of type 2 diabetes. Since its mechanism of action is independent of pancreatic islet b-cell function or the degree of insulin resistance. Therefore, SGLT2 inhibitors can be used not only alone, but also in combination with any of the existing glucose-lowering drugs, including insulin.

The Uses of Empagliflozin

Empagliflozin is a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats.

Indications

Empagliflozin is indicated for the following conditions:
(1) For improving glycaemic control in adults with type 2 diabetes mellitus in combination with diet and exercise. It can be used alone or in combination with metformin or linagliptin.
(2) For reducing the risk of cardiovascular death in adult patients with both type 2 diabetes and established cardiovascular disease, either alone or in combination with metformin.
(3) For sustained decline in eGFR, end-stage renal disease, cardiovascular death and risk of hospitalisation in adult patients with chronic kidney disease at risk of progression.
Empagliflozin is not approved for use in patients with type 1 diabetes.

Mechanism of action

Empagliflozin works by inhibiting the sodium-glucose co-transporter-2 (SGLT-2) found in the proximal tubules in the kidneys. Through SGLT2 inhibition, empagliflozin reduces renal reabsorption of glucose and increases urinary excretion of glucose.

Metabolism

Empagliflozin undergoes minimal metabolism. It is primarily metabolized via glucuronidation by 5'-diphospho-glucuronosyltransferases 2B7, 1A3, 1A8, and 1A9 to yield three glucuronide metabolites: 2-O-, 3-O-, and 6-O-glucuronide. No metabolite represented more than 10% of total drug-related material.