TRAJENTA 5 MG

Indications

• Type 2 diabetes mellitus as monotherapy
• Type 2 diabetes mellitus in combination with metformin
• Type 2 diabetes mellitus in combination with insulin
• Type 2 diabetes mellitus not controlled by metformin alone or in combination with other antidiabetic drugs

Dosage

Adults: The usual adult dose is 5 mg once daily, with or without food. Dosing may vary based on the patient's current metformin dose or when used

Mechanism of action

Linagliptin is a competitive, reversible inhibitor of the DPP-4 enzyme. By inhibiting DPP-4, linagliptin slows the breakdown of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Elevated levels of these hormones lead to increased insulin secretion from pancreatic beta cells and reduced glucagon secretion, facilitating a reduction in hepatic glucose output and improved glucose homeostasis.

Pharmacodynamics

A 5 mg oral dose of linagliptin achieves over 80% inhibition of DPP-4 for at least 24 hours. This sustained inhibition results in increased concentrations of GLP-1, which is associated with decreased levels of glycosylated hemoglobin and lower fasting plasma glucose levels, contributing to enhanced glycemic control in patients with type 2 diabetes.

Pharmacokinetics

Linagliptin is well-absorbed after oral administration, with peak plasma concentrations occurring within 1.5 hours. Its bioavailability is approximately 30%, and it has a long half-life of about 12 hours, allowing for once-daily dosing. Linagliptin is primarily excreted unchanged in the feces, with minimal renal clearance, making it suitable for patients with varying degrees of renal function. No dose adjustment is needed for mild to moderate renal impairment.

Contra-indications

• Hypersensitivity to linagliptin or any excipients
• Severe renal impairment (eGFR < 30 mL/min)

Adverse effects

• Hypoglycaemia
• Nausea
• Diarrhea
• Abdominal pain
• Pancreatitis
• Headache
• Upper respiratory tract infections

Interactions

• Linagliptin may increase exposure to lomitapide
• Mitotane may decrease exposure to linagliptin
• Concomitant use with sulfonylureas or insulin may increase risk of hypoglycaemia

Precautions

• Monitor renal function before and during treatment
• History of pancreatitis
• Assess for signs of allergic reactions

Pregnancy

No adequate data on the use of linagliptin during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether linagliptin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store below 30 degrees Celsius in a dry place. Keep out of reach of children.

Formulations

• Linagliptin 5 mg tablets (Trajenta)
• Linagliptin with metformin 2.5 mg/850 mg tablets (Jentadueto)

Mechanism of action

Linagliptin is a competitive, reversible DPP-4 inhibitor. Inhibition of this enzyme slows the breakdown of GLP-1 and glucose-dependant insulinotropic polypeptide (GIP). GLP-1 and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic beta cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose. 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.

Pharmacodynamics

A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose.