Exenatide: Difference between revisions
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MDElliottMD (talk | contribs) Create Exenatide page (initial draft, MedTemplate, full inline cites) |
MDElliottMD (talk | contribs) Fix Cargo VARCHAR(300) overflow: blank structure, shorten mechanism, move chemistry/mechanism prose to PK/PD |
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| generic = Exenatide | | generic = Exenatide | ||
| brand = Byetta (twice-daily), Bydureon BCise (weekly) | | brand = Byetta (twice-daily), Bydureon BCise (weekly) | ||
| structure = | | structure = | ||
| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · First-in-class incretin mimetic | | classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · First-in-class incretin mimetic | ||
| mechanism = | | mechanism = Agonist of the [[GLP-1 receptor]]; exendin-4 derivative from Gila monster venom. | ||
| uses = [[Type 2 diabetes mellitus]] (adjunct, second-line) | | uses = [[Type 2 diabetes mellitus]] (adjunct, second-line) | ||
| starting_dose = Byetta: 5 µg SC twice daily, within 60 min before morning and evening meals<ref name="byetta-label">US FDA. ''Byetta (exenatide) prescribing information.'' AstraZeneca. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf</ref> · Bydureon BCise: 2 mg SC once weekly<ref name="bydureon-label">US FDA. ''Bydureon BCise (exenatide extended-release) prescribing information.'' AstraZeneca. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209210s000lbl.pdf</ref> | | starting_dose = Byetta: 5 µg SC twice daily, within 60 min before morning and evening meals<ref name="byetta-label">US FDA. ''Byetta (exenatide) prescribing information.'' AstraZeneca. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf</ref> · Bydureon BCise: 2 mg SC once weekly<ref name="bydureon-label">US FDA. ''Bydureon BCise (exenatide extended-release) prescribing information.'' AstraZeneca. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209210s000lbl.pdf</ref> | ||
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In contrast to the long-acting weekly agents that followed, exenatide carries a heavier GI side-effect burden (especially Byetta BID) and is associated with anti-exenatide antibody formation in a substantial minority of users — antibodies that can reduce efficacy.<ref name="byetta-label"/> Twice-daily Byetta was discontinued in the United States in 2024.{{Citation needed}} Bydureon BCise remains available but is no longer commonly prescribed first-line. | In contrast to the long-acting weekly agents that followed, exenatide carries a heavier GI side-effect burden (especially Byetta BID) and is associated with anti-exenatide antibody formation in a substantial minority of users — antibodies that can reduce efficacy.<ref name="byetta-label"/> Twice-daily Byetta was discontinued in the United States in 2024.{{Citation needed}} Bydureon BCise remains available but is no longer commonly prescribed first-line. | ||
| pharmacokinetics = '''Byetta''' (BID): rapid absorption, peak ~2.1 h, half-life ~2.4 h. Renal elimination predominates (unlike most other GLP-1 RAs); dose adjustment required for CrCl 30–50, contraindicated <30.<ref name="byetta-label"/> | | pharmacokinetics = '''Chemistry'''. '''Exendin-4''' — a 39-amino-acid peptide originally isolated from the saliva of the Gila monster (''[[Heloderma suspectum]]''). Only 53% homologous with human [[GLP-1]] but naturally resistant to [[DPP-4]] cleavage because of a glycine at position 2.<ref name="eng1992">Eng J, Kleinman WA, Singh L et al. (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from ''Heloderma suspectum'' venom. ''J Biol Chem'' 267(11):7402–5.</ref> | ||
'''Byetta''' (BID): rapid absorption, peak ~2.1 h, half-life ~2.4 h. Renal elimination predominates (unlike most other GLP-1 RAs); dose adjustment required for CrCl 30–50, contraindicated <30.<ref name="byetta-label"/> | |||
'''Bydureon BCise''' (weekly): exenatide is encapsulated in slow-release biodegradable polymer microspheres; multiple peaks occur as successive microsphere cohorts release the peptide. Steady-state plasma levels are reached only after 6–7 weeks of weekly dosing — meaning early efficacy looks weaker than other weekly GLP-1 RAs.<ref name="bydureon-label"/> | '''Bydureon BCise''' (weekly): exenatide is encapsulated in slow-release biodegradable polymer microspheres; multiple peaks occur as successive microsphere cohorts release the peptide. Steady-state plasma levels are reached only after 6–7 weeks of weekly dosing — meaning early efficacy looks weaker than other weekly GLP-1 RAs.<ref name="bydureon-label"/> | ||
| pharmacodynamics = At maintenance doses: | | pharmacodynamics = '''Receptor pharmacology'''. Selective agonist of the [[GLP-1 receptor]]. Mechanism identical to other GLP-1 RAs (glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression).<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351.</ref> | ||
At maintenance doses: | |||
* HbA1c reduction of ~0.8–1.0 percentage points (Byetta 10 µg BID or Bydureon 2 mg/wk)<ref name="byetta-label"/><ref name="bydureon-label"/> | * HbA1c reduction of ~0.8–1.0 percentage points (Byetta 10 µg BID or Bydureon 2 mg/wk)<ref name="byetta-label"/><ref name="bydureon-label"/> | ||
* Weight loss of ~2–3 kg<ref name="byetta-label"/> | * Weight loss of ~2–3 kg<ref name="byetta-label"/> | ||