Liraglutide
- Atc Codes:A10BX07
- CAS Codes:204656-20-2
- PHARMGKB ID:204656-20-2
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Genes that may be involved
- Drug Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Victoza; Belgium: Victoza; Bulgaria: Victoza; Czech Republic: Victoza; Denmark: Victoza; Estonia: Victoza; Finland: Victoza; France: Victoza; Germany: Victoza; Greece: Victoza; Hungary: Victoza; Ireland: Victoza; Italy: Victoza; Latvia: Victoza; Lithuania: Victoza; Luxembourg: Victoza; Malta: Victoza; Netherlands: Victoza; Poland: Victoza; Portugal: Victoza; Romania: Victoza; Slovakia: Victoza; Slovenia: Victoza; Sweden: Victoza; UK: Victoza.
North America
Canada: Victoza; USA: Victoza.
Drug combinations
Chemistry
Liraglutide: C~172~H~265~N~43~O~51~. Mw: 3751.2. (1) L-histidyl-L-alanyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-valyl-L-seryl-L-seryl-L-tyrosyl-L-leucyl-L-α-glutamylglycyl-L-glutaminyl-L-alanyl-L-alanyl-N^6^-[N-(1-oxohexadecyl)-L-γ-glutamyl]-L-lysyl-L-α-glutamyl-L-phenylalanyl-L-isoleucyl-L-alanyl-L-tryptophyl-L-leucyl-L-valyl-L-arginylglycyl-L-arginyl-glycine; (2) Arg34Lys26-(N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1[7-37]. CAS-204656-20-2.
Pharmacologic Category
Other Antidiabetic Agents; Analog of Human GLP-1, GLP-1 Receptor Agonist. (ATC-Code: A10BX07).
Mechanism of action
Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) receptor agonist with 97% aa sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP), leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying. GLP-1(7-37) has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once daily administration, is a result of self-association that delays absorption, plasma protein binding and stability against metabolic degradation by DPP-IV and NEP.
Therapeutic use
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Pregnancy and lactiation implications
Liraglutide has been shown to be teratogenic in animals; should be used during pregnancy only if potential benefit justifies potential risk to fetus. Because of the potential for tumorigenicity shown for liraglutide in animal studies, a decision should be made whether to discontinue nursing or to discontinue treatment, taking into account the importance of the drug to the mother.
Unlabeled use
Contraindications
Do not use in patients with personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.
Warnings and precautions
Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in rodents. It is unknown whether it causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies. Contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. Increased cases of pancreatitis were observed (use with caution in patients with history of pancreatitis). Liraglutide is not a substitute for insulin (should not be used in patients with type 1 diabetes mellitus or for treatment of diabetic ketoacidosis). The concurrent use of liraglutide and insulin has not been studied. Serious hypoglycemia can occur in combination with an insulin secretagog (e.g. a sulfonylurea)(consider lowering the dose of the insulin secretagog to reduce the risk of hypoglycemia). There have been no studies establishing conclusive evidence of macrovascular risk reduction with liraglutide or any other antidiabetic drug.