依帕列净, Empagliflozin

Inhibiting renal glucose reabsorption through the sodium-glucose cotransporter (SGLT) offers an insulin-independent alternative to controlling blood glucose concentrations in patients with type 2 diabetes. The majority of glucose is reabsorbed from glomerular filtrate by SGLT2, which is predominantly expressed in the kidney S1 segment of the proximal tubule. Empagliflozin is a potent SGLT2 inhibitor (IC50 = 3.1 nM) that demonstrates a high degree of selectivity (>2,500-fold) over SGLT1, 4, 5, and 6.3 In clinical trials of patients with type 2 diabetes, empagliflozin was shown to lower fasting and postprandial glucose levels by increasing total glucose excretion, improving β-cell function, and shifting substrate utilization from glucose to lipids.

Empagliflozin is an orally available competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2; SLC5A2) with antihyperglycemic activity. Upon oral administration, empagliflozin selectively and potently inhibits SGLT2 in the kidneys, thereby suppressing the reabsorption of glucose in the proximal tubule. Inhibition of SGLT2 increases urinary glucose excretion by the kidneys, resulting in a reduction of plasma glucose levels in an insulin-independent manner. SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.

Empagliflozin is a C-glycosyl compound consisting of a beta-glucosyl residue having a (4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl group at the anomeric centre. A sodium-glucose co-transporter 2 inhibitor used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It has a role as a sodium-glucose transport protein subtype 2 inhibitor and a hypoglycemic agent. It is a C-glycosyl compound, an aromatic ether, a tetrahydrofuryl ether and a member of monochlorobenzenes.

Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies, for the management of type 2 diabetes mellitus. The first known inhibitor of SGLTs, phlorizin, was isolated from the bark of apple trees in 1835 and researched extensively into the 20th century, but was ultimately deemed inappropriate for clinical use given its lack of specificity and significant gastrointestinal side effects. Attempts at overcoming these limitations first saw the development of O-glucoside analogs of phlorizin (e.g. [remogliflozin etabonate]), but these molecules proved relatively pharmacokinetically unstable. The development of C-glucoside phlorizin analogs remedied the issues observed in the previous generation, and led to the FDA approval of [canagliflozin] in 2013 and both [dapagliflozin] and empagliflozin in 2014. As the most recently approved of the "flozin" drugs, empagliflozin carries the highest selectivity for SGLT2 over SGLT1 (approximately 2700-fold).

Potent, selective and competitive inhibitor of sodium-glucose cotransporter SGLT2, which is implicated in renal glucose reabsorption. The compound increases urinary glucose excretion, helps decrease hyperglyceamia and maintains glucose homeostasis in diabetic individuals. It has been associated with weight loss, lower blood pressure and decreased glycated haemoglobin. Animal studies suggest that empagliflozin preserves regeneration of β-cells in pancreatic Langerhans islets.