Combination of Linagliptin, a DPP-4 inhibitor & Metformin, a member of the biguanide class) with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus.
Linagliptin: Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.
Metformin: Metformin lowers both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglyceamia or increased weight gain. Metformin may exert its glucose-lowering effect via four mechanisms:
by reduction of hepatic glucose production through inhibition of gluconeogenesis and glycogenolysis;
in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and utilization;
by delaying intestinal glucose absorption;
stimulate intracellular glycogen synthesis by acting on glycogen synthase and increase the transport capacity of glucose transporters (GLUT-1 & GLUT-4)