Empagliflozin; Linagliptin

Empagliflozin/Linagliptin is a fixed dose combination of empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2; SLC5A2), and linagliptin, a dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with antihyperglycemic activity. Upon oral administration of empagliflozin/linagliptin, 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. Linagliptin binds to and inhibits DPP-4, thereby inhibiting the breakdown of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This prolongs the activity of these incretin hormones, increases postprandial insulin secretion from pancreatic beta cells, decreases glucagon secretion and lowers blood glucose levels. SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid. DPP-4 is a serine protease that degrades the incretin hormones GLP-1 and GIP, which play important roles in the regulation of glucose homeostasis.