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| Primary information |
|---|
| ID | 10604 |
| Therapeutic ID | Th1124 |
| Protein Name | Liraglutide |
| Sequence | >Th1124_Liraglutide
HAEGTFTSDVSSYLEGQAAKEEFIAWLVRGRG
|
| Molecular Weight | 3751.2 |
| Chemical Formula | C172H265N43O51 |
| Isoelectric Point | 4.9 |
| Hydrophobicity | NA |
| Melting point | NA |
| 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 | There is no clinical significance of race or ethnicity on the safety or efficacy of liraglutide[Label]. Geriatric patients do not experience clinically significant differences in pharmacokinetics though patients at an especially advanced age may be more susceptible to adverse effects[Label]. Female patients have reduced clearance of liraglutide but no dose adjustment is necessary[Label]. The risk and benefit of liraglutide in pregnancy must be weighed before prescribing[Label]. In animal studies, liraglutide is associated with an increased risk of embryonic death and fetal abnormalities though an HbA1c > 7 is also associated with a 20-25% risk of birth defects[Label]. In animal studies, liraglutide is present in the milk of lactating rats at half the plasma concentration of the mother but these results may not translate to humans[Label]. Because it is not known if liraglutide is present in breast milk and the effects on infants are also unknown, the risk and benefit of liraglutide in breastfeeding must be considered before prescribing[Label]. Liraglutide was shown to be safe and effective in patients up to 160kg in weight but has not been studied in patients at a higher weight[Label]. A patient's weight significantly affects the pharmacokinetics of liraglutide[Label]. Liraglutide has not been investigated for use in pediatric patients[Label]. No dosage adjustments are necessary in patients with renal impairment but studies have not been performed in patients with end stage renal disease[Label]. There are no recommendations on dosage adjustment in patients with hepatic impairment, though caution should still be exercised when prescribing to this population[Label]. |
| Metabolism | Liraglutide is less sensitive to metabolism than the endogenous GLP-1 and so is more slowly metabolized by dipeptidyl peptidase-4 and neutral endopeptidase to various smaller polypeptides which have not all been structurally determined[A6932]. A portion of Liraglutide may be completely metabolized to carbon dioxide and water[A6932]. |
| Absorption | Bioavailability of liraglutide after subcutaneous injection is approximately 55%[Label] and maximum concentrations are reached after 11.7 hours[A6932]. |
| 13L[Label]. |
| Clearance | 1.2L/h[Label]. |
| Categories | NA |
| Patents Number | US6268343 |
| Date of Issue | 31-07-2001 |
| Date of Expiry | 22-02-2023 |
| Drug Interaction | NA |
| Target | Glucagon-like peptide 1 receptor |
| Brand Name | Saxenda |
| Company | Novo Nordisk |
| Brand Description | Novo Nordisk |
| Prescribed For | obese |
| Chemical Name | NA |
| 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). |
| Physical Appearance | 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 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |