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Identification
NameLiraglutide
Accession NumberDB06655
TypeBiotech
GroupsApproved
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 structureNo structure small
Related Articles
Protein chemical formulaC172H265N43O51
Protein average weight3751.2 Da
Sequences
>results for sequence "results for sequence "victoza"" starting "HisAlaGluGly"
HAEGTFTSDVSSYLEGQAAKEEFIIAWLVKGRG
Download FASTA Format
Synonyms
Arg34Lys26-(N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1[7-37]
Liraglutida
Liraglutide recombinant
Liraglutidum
N²⁶-(hexadecanoyl-gamma-glutamyle)-[34-arginine]GLP-1-(7-37)-peptide
N²⁶-(N-Hexadecanoyl-L-gamma-glutamyl)-[34-L-arginine]glucagon-like peptide 1-(7-37)-peptide
NN 2211
NN-2211
NN2211
NNC 90-1170
Victoza
External Identifiers
  • NN 2211
  • UNII-839I73S42A
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Saxendainjection, solution6 mg/mLsubcutaneousNovo Nordisk2014-12-31Not applicableUs
Saxendasolution6 mgsubcutaneousNovo Nordisk Canada Inc2015-05-27Not applicableCanada
Victozasolution6 mgsubcutaneousNovo Nordisk Canada Inc2010-05-27Not applicableCanada
Victozainjection, solution6 mg/mLsubcutaneousNovo Nordisk2010-01-25Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII839I73S42A
CAS number204656-20-2
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor use in/treatment of diabetes mellitus type 2.
PharmacodynamicsLiraglutide 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 actionLiraglutide 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.
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AbsorptionMaximum 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 eliminationExcreted in urine and feces, 6% and 5%, respectively.
Half lifeapproximately 13 hours.
Clearance

The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h

ToxicityIn 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionsubcutaneous6 mg/mL
Solutionsubcutaneous6 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2264243 No2004-10-052017-08-22Canada
US6004297 No1999-01-282019-01-28Us
US6268343 No2002-08-222022-08-22Us
US6458924 No1997-08-222017-08-22Us
US6899699 No2002-01-012022-01-01Us
US7235627 No1997-08-222017-08-22Us
US7686786 No2006-08-032026-08-03Us
US8114833 No2005-08-132025-08-13Us
US8672898 No2002-01-022022-01-02Us
US8684969 No2005-10-202025-10-20Us
US8846618 No2002-06-272022-06-27Us
US8920383 No2006-07-172026-07-17Us
US9108002 No2006-01-262026-01-26Us
US9132239 No2012-02-012032-02-01Us
US9265893 No2012-09-232032-09-23Us
USRE41956 No2001-01-212021-01-21Us
USRE43834 No1999-01-282019-01-28Us
Properties
StateLiquid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  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. doi: 10.1016/j.mce.2008.11.018. Epub 2008 Nov 25. [PubMed:19041364 ]
  2. Vilsboll T: Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc). 2009 Feb;45(2):101-13. doi: 10.1358/dot.2009.45.2.1336104. [PubMed:19343230 ]
  3. Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, Helleberg H, Larsen U, Oosterhuis B, van Lier JJ, Zdravkovic M, Olsen AK: Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53. doi: 10.1124/dmd.110.034066. Epub 2010 Aug 13. [PubMed:20709939 ]
  4. Link [Link]
External Links
ATC CodesA10AE56A10BX07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (273 KB)
MSDSDownload (569 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Liraglutide.
ChlorpropamideLiraglutide may increase the hypoglycemic activities of Chlorpropamide.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Liraglutide.
Insulin AspartLiraglutide may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecLiraglutide may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirLiraglutide may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineLiraglutide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineLiraglutide may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanLiraglutide may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproLiraglutide may increase the hypoglycemic activities of Insulin Lispro.
LeuprolideThe therapeutic efficacy of Liraglutide can be decreased when used in combination with Leuprolide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Liraglutide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Liraglutide.
ParoxetineParoxetine may increase the hypoglycemic activities of Liraglutide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Liraglutide.
PhenelzinePhenelzine may increase the hypoglycemic activities of Liraglutide.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Liraglutide.
TestosteroneTestosterone may increase the hypoglycemic activities of Liraglutide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Liraglutide.
TrichlormethiazideThe therapeutic efficacy of Liraglutide can be decreased when used in combination with Trichlormethiazide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Transmembrane signaling receptor activity
Specific Function:
This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
GLP1R
Uniprot ID:
P43220
Molecular Weight:
53025.22 Da
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:14678021 ]
  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. doi: 10.1111/j.1463-1326.2008.00865.x. [PubMed:18333889 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Virus receptor activity
Specific Function:
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also ...
Gene Name:
DPP4
Uniprot ID:
P27487
Molecular Weight:
88277.935 Da
References
  1. Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, Helleberg H, Larsen U, Oosterhuis B, van Lier JJ, Zdravkovic M, Olsen AK: Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53. doi: 10.1124/dmd.110.034066. Epub 2010 Aug 13. [PubMed:20709939 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Zinc ion binding
Specific Function:
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of at...
Gene Name:
MME
Uniprot ID:
P08473
Molecular Weight:
85513.225 Da
References
  1. Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, Helleberg H, Larsen U, Oosterhuis B, van Lier JJ, Zdravkovic M, Olsen AK: Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53. doi: 10.1124/dmd.110.034066. Epub 2010 Aug 13. [PubMed:20709939 ]
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Drug created on March 19, 2008 10:45 / Updated on July 27, 2016 02:05