ALOGLIPTIN AND METFORMIN HYDROCHLORIDE

12.1 Mechanism of Action Alogliptin and Metformin HCl Alogliptin and metformin HCl tablets combine two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: alogliptin, a selective inhibitor of DPP-4, and metformin HCl, a member of the biguanide class. Alogliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogli

Contraindications

• • including diabetic ketoacidosis with or without coma. History of serious hypersensitivity reaction to alogliptin or metformin or any of the excipients
• • such as anaphylaxis
• • angioedema and severe cutaneous adverse reactions [see Warnings and Precautions (5.4)
• • Adverse Reactions (6.2) ] . Severe renal impairment: eGFR below 30 mL/min/1.73 m 2 . ( 4 ) Metabolic acidosis
• • including diabetic ketoacidosis. ( 4 ) History of serious hypersensitivity to alogliptin or metformin or any of the excipients. ( 4 )