| Primary information |
|---|
| ThPP ID | Th1124 |
| Therapeutic Peptide/Protein Name | Liraglutide |
| Sequence | HAEGTFTSDVSSYLEGQAAKEEFIIAWLVKGRG view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 3751.2 |
| Chemical Formula | C172H265N43O51 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | approx. 13 hrs |
| Description | Contains liraglutide, an analog of human GLP-1, and acts as a GLP-1 receptor agonist. The recombinant peptide precursor of liraglutide, produced by its expression in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting R for K at position 34. Liraglutide was designed 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. |
| Indication/Disease | 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. |
| 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 |
| 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. |
| 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 13LIntravenous is approximately 0.07L/kg |
| Clearance | The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h |
| Categories | N.A. |
| Patents Number | US6268343 |
| Date of Issue | 23/08/01 |
| Date of Expiry | 23/08/21 |
| Drug Interaction | N.A. |
| Target | Glucagon-like peptide 1 receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Saxenda |
| Company | Novo Nordisk |
| Brand Discription | Saxenda 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. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. |
| Prescribed for | obese |
| Chemical Name | N.A. |
| Formulation | Each 1 mL of Saxenda solution contains 6 mg of liraglutide and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. Each pre-filled pen contains a 3 mL solution of Saxenda equivalent to 18 mg liraglutide (free-base, anhydrous). |
| Physcial Appearnce | Saxenda is a clear, colorless solution |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 3 mg daily |
| Contraindication | medullary thyroid carcinoma, Multiple Endocrine Neoplasia syndrome type 2 , hypersensitivity, Pregnancy |
| Side Effects | Risk of Thyroid C-Cell Tumors, Acute Pancreatitis, Acute Gallbladder, Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy , Heart Rate Increase, Renal Impairment, Hypersensitivity Reactions, Suicidal Behavior and Ideation. |
| Useful Link | http://www.rxlist.com/saxenda-drug.htm https://www.saxenda.com/ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm |
| PubMed ID | 25656058, 25650514, 25626486, 25625650, 25619391, 25614699, 20709939, 19343230, 19041364 |
| 3-D Structure | Th1124 (View) or (Download) |