Indications
This is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate.
Therapeutic Class
Combination Oral hypoglycemic preparations
Pharmacology
Ccombination 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)
Dosage & Administration
The dosage should be individualized on the basis of both effectiveness and tolerability. Maximum recommended dose of 2.5 mg Linagliptin and 1000 mg Metformin Hydrochloride twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with Metformin use.Recommended starting dose: In patients currently not treated with Metformin, initiate treatment with 2.5 mg Linagliptin and 500 mg Metformin Hydrochloride twice daily. In patients already treated with Metformin, start with 2.5 mg Linagliptin and the current dose of Metformin Hydrochloride twice daily. Patients already treated with linagliptin and metformin, individual components may be switched to this combination containing the same doses of each component.
Interaction
Cationic drugs (amiloride, digoxin, morphine, ranitidine, trimethoprim etc.): May reduce metformin elimination. P-glycoprotien/CYP3A4 inducer (i.e. rifampin): The efficacy of this medicine may be reduced when administered in combination.
Contraindications
Although Linagliptin undergoes minimal renal excretion, Metformin is known to be substantially excreted by the kidney. The risk of Metformin accumulation and lactic acidosis increases with the degree of renal impairment. Therefore, this combination is contraindicated in patients with renal impairment. It is also contraindicated in acute or chronic metabolic acidosis (diabetic ketoacidosis) and in hypersensitivity to Linagliptin or Metformin.
Side Effects
Most common side effects are nasopharyngitis and diarrhea. Hypoglycemia is more common in patients treated with this combination and sulfonylureas.
Pregnancy & Lactation
Pregnancy category B. There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother
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