Exenatide — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Exenatide, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GLP-1 receptor (GLP1R) | Full agonist | Ki ≈ 2.5 nM; slower receptor dissociation than native GLP-1 |
§2.2Mechanism of action
Exenatide is a naturally DPP-4-resistant GLP-1 receptor agonist. The immediate-release presentation gives short, high peaks that produce a pronounced effect on gastric emptying and postprandial glucose but a modest effect on fasting glucose. The extended-release presentation, in which peptide is encapsulated in biodegradable microspheres, gives continuous exposure with a different pharmacodynamic emphasis: greater HbA1c reduction, less postprandial specificity, and reduced nausea.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈2.4 h (immediate release); apparent 2 weeks for the microsphere product driven by release rate
- Time to maximum concentration
- ≈2.1 h (immediate release); biphasic at 2 and 6–7 weeks (extended release)
- Volume of distribution
- ≈28.3 L
- Plasma protein binding
- not extensively bound
- Clearance
- ≈9.1 L/h
- Bioavailability
- not formally reported
Predominantly glomerular filtration with subsequent proteolysis. Clearance falls markedly in severe renal impairment and the product is not recommended below an eGFR of 30 mL/min/1.73 m².
§2.4Interactions
- Warfarin — INR increase reported
- Oral medicines with narrow absorption windows — administer at least 1 hour before exenatide immediate release
- Insulin secretagogues — hypoglycaemia
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.
- Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917 · PMID 28910237
- Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0 · PMID 19515413
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.