Liraglutide — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Liraglutide, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GLP-1 receptor (GLP1R) | Full agonist | Affinity approximately 0.11 nM; albumin binding reduces free fraction |
| Albumin (non-receptor) | Reversible binding via palmitoyl chain | 98–99 % bound; also promotes heptamer self-association at the injection depot, slowing absorption |
§2.2Mechanism of action
Receptor pharmacology is that of the selective GLP-1 class. The pharmacokinetic engineering differs: self-association into heptamers at the subcutaneous depot slows absorption, and albumin binding through the palmitoyl chain limits renal clearance and protects against DPP-4. The net effect is a 13-hour half-life supporting once-daily administration.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈13 h
- Time to maximum concentration
- 8–12 h
- Volume of distribution
- ≈13 L (subcutaneous), 0.07 L/kg intravenous
- Plasma protein binding
- >98 % (albumin)
- Clearance
- ≈1.2 L/h
- Bioavailability
- ≈55 % absolute bioavailability
Endogenous proteolysis by DPP-4 and neutral endopeptidase after dissociation from albumin, with no single organ identified as the principal route of elimination. Less than 6 % of the dose appears as metabolite in urine and about 5 % in faeces.
§2.4Interactions
- Insulin and secretagogues — hypoglycaemia
- Delayed gastric emptying may alter absorption rate of oral medicines
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DCW, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JPH. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine 2015;373(1):11–22. doi:10.1056/NEJMoa1411892 · PMID 26132939
- Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2016;375(4):311–322. doi:10.1056/NEJMoa1603827 · PMID 27295427
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.