Products
Linagliptin has been registered as a film-coated tablet in the United States and EU since 2011 and in many countries since 2012 (Trajenta). It went on sale in many countries on May 1, 2012. Linagliptin is also combined fixed with metformin as well as with empagliflozin. Trijardy XR is a fixed combination of empagliflozin, linagliptin, and metformin.
Structure and Properties
Linagliptin (C25H28N8O2, Mr = 472.5 g/mol) is a xanthine derivative. It is a white to yellowish and somewhat hygroscopic substance, soluble in water to 0.9 mg/ml.
Effects
Linagliptin (ATC A10BH05) has antidiabetic properties. The effects are due to selective and reversible inhibition of dipeptidyl peptidase-4 (DPP-4). Linagliptin promotes insulin synthesis and release from pancreatic beta cells, improves beta cell sensitivity to glucose, and increases its uptake into tissues. It reduces glucagon secretion from alpha cells, resulting in decreased glucose production in the liver see under gliptins
Indications
For the treatment of type 2 diabetes mellitus. Linagliptin may be combined with other oral antidiabetic agents such as metformin, sulfonylureas, and glitazones.
Dosage
According to the drug label. The usual dose is 5 mg regardless of meals. Due to its long half-life of over 100 hours, once-daily administration is sufficient.
Contraindications
- Hypersensitivity
Linagliptin is not indicated for the treatment of type 1 diabetes and has not been studied in combination with insulins. Full precautionary information under Interactions can be found in the drug label.
Interactions
Linagliptin is excreted predominantly unchanged in the feces (90%). It is a substrate of P-glycoprotein and a weak to moderate inhibitor of CYP3A4. P-gp inducers such as rifampicin may therefore lead to inactivation of the drug.
Adverse effects
Possible adverse effects of monotherapy or combination therapy include nasopharyngitis, hyperlipidemia, cough, weight gain, hypersensitivity reactions, headache, and muscle and joint pain. Rare cases of pancreatitis have been reported. Hypoglycemia occurs primarily in combination with sulfonylureas.
