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Identification
Name Liraglutide
Accession Number DB06655
Type biotech
Groups approved
Description

Victoza contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor.
Protein structure No_structure_small
Protein chemical formula C172H265N43O51
Protein average weight 3751.2 Da
Sequences 
>results for sequence "results for sequence "victoza"" starting "HisAlaGluGly"
HAEGTFTSDVSSYLEGQAAKEEFIIAWLVKGRG

FASTA
Synonyms
Arg34Lys26-(N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1[7-37]
NN 2211
NN2211
Salts Not Available
Brand names
Name Company
Victoza Novo Nordisk
Brand mixtures Not Available
Categories
  • Glucagon-like peptide-1 [GLP-1] receptor agonist
CAS number 204656-20-2
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For use in/treatment of diabetes mellitus type 2.
Pharmacodynamics Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2 diabetes. GLP-1, in its natural form, is short-lived in the body (the half-life after subcutaneous injection is approximately one hour), so it is not very useful as a therapeutic agent. However, liraglutide has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing. The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1 molecule, enabling it to bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Binding with albumin also results in slower degradation and reduced elimination of liraglutide from the circulation by the kidneys compared to GLP-1.
Mechanism of action Liraglutide is an acylated GLP-1 (Glucagon-Like Peptide-1) receptor agonist. Liraglutide upregulates intracellular cAMP resulting in the release of insulin given elevated blood glucose concentrations. Glucagon secretion is also decreased in a glucose-dependent fashion by liraglutide.
Absorption Maximum concentrations of liraglutide are achieved at 8-12 hours after dose. The mean peak and total exposures of liraglutide were 35 ng/mL and 960 ng·h/mL, respectively, for a subQ single dose of 0.6 mg. After subcutaneous single dose administrations, Cmax and AUC of liraglutide increased proportionally over the therapeutic dose range of 0.6 mg to 1.8 mg. At 1.8 mg Victoza, the average steady state concentration of liraglutide over 24 hours was approximately 128 ng/mL. AUC0-∞ was equivalent between upper arm and abdomen, and between upper arm and thigh. AUC0-∞ from thigh was 22% lower than that from abdomen. Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.
Volume of distribution

SubQ 0.6 mg is approximately 13L
Intravenous is approximately 0.07L/kg
Protein binding >98%
Metabolism During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.
Route of elimination Not Available
Half life approximately 13 hours.
Clearance

The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h
Toxicity In a clinical trial, one patient with type 2 diabetes experienced a single overdose of Victoza 17.4 mg subcutaneous (10 times the maximum recommended dose). Effects of the overdose included severe nausea and vomiting requiring hospitalization. No hypoglycemia was reported. The patient recovered without complications. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. RISK OF THYROID C-CELL TUMORS
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novo nordisk inc
Packagers Not Available
Dosage forms
Form Route Strength
Injection Subcutaneous Multi-dose pen (0.6 mg, 1.2 mg, or 1.8 mg [6 mg/mL, 3 mL])
Prices Not Available
Patents
Country Patent Number Approved Expires (estimated)
United States 6268343 1997-08-22 2017-08-22
Canada 2264243 2004-10-05 2017-08-22
Properties
State liquid
Experimental Properties Not Available
References
Synthesis Reference Not Available
General Reference
  1. Russell-Jones D: Molecular, pharmacological and clinical aspects of liraglutide, a once-daily human GLP-1 analogue. Mol Cell Endocrinol. 2009 Jan 15;297(1-2):137-40. Epub 2008 Nov 25. Pubmed
  2. Vilsboll T: Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc). 2009 Feb;45(2):101-13. Pubmed
  3. http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15776
External Links
Resource Link
PharmGKB PA165958364 Link_out
RxList http://www.rxlist.com/victoza-drug.htm Link_out
Drugs.com http://www.drugs.com/cdi/liraglutide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Liraglutide Link_out
ATC Codes
  • A10BX07
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of liraglutide. Monitor for changes in fasting and postprandial blood sugars.
Food Interactions Not Available
Targets

1. Glucagon-like peptide 1 receptor

Pharmacological action: yes
Actions: agonist

This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P43220 Link_out
Gene: GLP1R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bock T, Pakkenberg B, Buschard K: The endocrine pancreas in non-diabetic rats after short-term and long-term treatment with the long-acting GLP-1 derivative NN2211. APMIS. 2003 Dec;111(12):1117-24. Pubmed
  2. Larsen PJ, Wulff EM, Gotfredsen CF, Brand CL, Sturis J, Vrang N, Knudsen LB, Lykkegaard K: Combination of the insulin sensitizer, pioglitazone, and the long-acting GLP-1 human analog, liraglutide, exerts potent synergistic glucose-lowering efficacy in severely diabetic ZDF rats. Diabetes Obes Metab. 2008 Apr;10(4):301-11. Pubmed
Comments
Drug created on March 19, 2008 10:45 / Updated on April 25, 2013 15:33