Linagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Linagliptin may be used as monotherapy or in combination with other common antidiabetic medications including Metformin, Sulfonylurea, Pioglitazone, or Insulin. As a replacement therapy it is suitable when Metformin therapy is not appropriate due to intolerance or do not provide adequate glycemic control as monotherapy or other antidiabetic drugs are to be discontinued due to renal or hepatic impairment.
Dipeptidyl Peptidase-4 (DPP-4) inhibitor
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). By inhibiting DPP-4 Linagliptin increases the concentrations of active incretin hormones and stimulates the release of Insulin in a glucose dependent manner and decreases the level of Glucagon in the circulation and thus regulates the 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 elevated blood glucose levels. Furthermore, GLP-1 also reduces Glucagon secretion from pancreatic alpha-cells, resulting in a reduction in hepatic glucose output.
The recommended dose of Linagliptin is 5 mg once daily and can be taken with or without food. If added with Metformin, the dose of Metformin should be maintained and Linagliptin administered concomitantly. When used in combination with Sulfonylurea, a lower dose of Sulfonylurea may be considered to reduce the risk of hypoglycemia.
Linagliptin doesn’t interact with Metformin, Glyburide, Simvastatin, Warfarin, Digoxin or oral contraceptives. Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. Again it doesn’t act as an inducer of CYP isozymes.
Linagliptin is contraindicated to patients hypersensitive to Linagliptin or any of the excipients.
Treatment with Linagliptin is well tolerated; some of the less common side effects are nasopharyngitis and hypoglycemia.
: There are no adequate and well-controlled studies in pregnant women. Linagliptin tablets should be used during pregnancy only if the potential benefit of mother justifies the potential risk of the fetus.
Nursing mothers: Caution should be exercised when Linagliptin is administered to a nursing woman.
When used with an Insulin secretagogue (e.g., sulfonylurea) or Insulin, consider lowering the dose of the Insulin secretagogue or Insulin to reduce the risk of hypoglycemia. If pancreatitis is suspected, Linagliptin should be discontinued. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Linagliptin or any other antidiabetic drug.
Pediatric patients: Safety and effectiveness of Linagliptin in patients below the age of 18 have not been established.
Renal or hepatic impairment: No dose adjustment required.
Store in a cool dry place protected from light. Keep out of reach of children.