Dulaglutide — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Dulaglutide, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GLP-1 receptor (GLP1R) | Agonist | Two GLP-1 moieties per molecule |
| Neonatal Fc receptor (FcRn) | Recycling ligand | Confers the extended half-life |
| Fcγ receptors | Deliberately attenuated | IgG4 Fc with substitutions to minimise effector function |
§2.2Mechanism of action
Receptor pharmacology is that of the selective GLP-1 class, delivered from a large fusion protein. Because the molecule is above the renal filtration threshold, clearance is not renal, and the pharmacokinetics are governed by FcRn-mediated recycling and reticuloendothelial catabolism.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈4.7 days
- Time to maximum concentration
- 24–72 h
- Volume of distribution
- ≈19.2 L (apparent, subcutaneous)
- Plasma protein binding
- not applicable in the small-molecule sense
- Clearance
- ≈0.111 L/h
- Bioavailability
- ≈47–65 % absolute bioavailability
Catabolism to constituent amino acids by general protein degradation pathways. No renal or hepatic elimination route is dose-limiting.
§2.4Interactions
- Insulin and secretagogues — hypoglycaemia
- Gastric emptying delay is modest relative to short-acting agents
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.
- Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet 2019;394(10193):121–130. doi:10.1016/S0140-6736(19)31149-3 · PMID 31189511
- Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology 2018;6(4):275–286. doi:10.1016/S2213-8587(18)30024-X · PMID 29397376
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.