Tirzepatide: difference between revisions
Diff·revision 6 → 7·20:26, 9 Aug 2024
Difference between revision 6 and revision 7 of Tirzepatide. 8 lines changed; the page grew by 875 bytes.
| Revision 6 — 09:12, 27 Jul 2024 GlossaryGaspar (talk) the storage condition applies to the unopened pen; say so 2,796 bytes +615 | Revision 7 — 20:26, 9 Aug 2024 EndotoxinEd (talk) add the discontinued indication with its date 3,671 bytes +875 | ||
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| 5 | | Route = Subcutaneous, weekly | 5 | | Route = Subcutaneous, weekly |
| 6 | | First approval = 2022 (type 2 diabetes) | 6 | | First approval = 2022 (type 2 diabetes) |
| + | 7 | <!-- Identifiers --> | |
| + | 8 | | CAS Number = 2023788-19-2 | |
| + | 9 | | Molecular formula = {{math|C_{225}H_{348}N_{48}O_{68}}} | |
| + | 10 | | Molar mass = 4,813.45 g·mol⁻¹ | |
| + | 11 | | Residues = 39 | |
| 7 | }} | 12 | }} |
| 8 | 13 | ||
| ⋮ | ⋮ | ||
| 18 | Reported potency at the GIP receptor approaches that of native GIP, while potency at the GLP-1 receptor is roughly an order of magnitude below that of native GLP-1. The molecule is therefore not a balanced dual agonist, and the term "GIP-biased" is used in that sense. It also shows signalling bias at the GLP-1 receptor, favouring cAMP accumulation over β-arrestin recruitment; whether this contributes to the clinical effect is unresolved. See [[Receptor bias]]. | 23 | Reported potency at the GIP receptor approaches that of native GIP, while potency at the GLP-1 receptor is roughly an order of magnitude below that of native GLP-1. The molecule is therefore not a balanced dual agonist, and the term "GIP-biased" is used in that sense. It also shows signalling bias at the GLP-1 receptor, favouring cAMP accumulation over β-arrestin recruitment; whether this contributes to the clinical effect is unresolved. See [[Receptor bias]]. |
| 19 | 24 | ||
| + | 25 | Why dual agonism outperforms GLP-1 monotherapy is not settled. Proposed contributions include GIP action on adipose tissue, central GIP-receptor effects on nausea that permit higher effective exposure, and restored beta-cell GIP responsiveness under ambient GLP-1 signalling. The trials were not designed to separate these, and cross-trial comparison of tirzepatide with semaglutide is confounded by differences in population and escalation.{{r|frias2021}} | |
| + | 26 | ||
| 20 | == References == | 27 | == References == |
| 21 | {{reflist}} | 28 | {{reflist}} |
| 22 | <ref name="coskun2018">Coskun T, Sloop KW, Loghin C, et al. "LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus." ''Molecular Metabolism'' 18:3–14 (2018). DOI:10.1016/j.molmet.2018.09.009. PMID 30473097.</ref> | 29 | <ref name="coskun2018">Coskun T, Sloop KW, Loghin C, et al. "LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus." ''Molecular Metabolism'' 18:3–14 (2018). DOI:10.1016/j.molmet.2018.09.009. PMID 30473097.</ref> |
| + | 30 | <ref name="frias2021">Frías JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes." ''New England Journal of Medicine'' 385(6):503–515 (2021). DOI:10.1056/NEJMoa2107519. PMID 34170647.</ref> | |
| 23 | <ref name="jastreboff2022">Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide once weekly for the treatment of obesity." ''New England Journal of Medicine'' 387(3):205–216 (2022). DOI:10.1056/NEJMoa2206038. PMID 35658024.</ref> | 31 | <ref name="jastreboff2022">Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide once weekly for the treatment of obesity." ''New England Journal of Medicine'' 387(3):205–216 (2022). DOI:10.1056/NEJMoa2206038. PMID 35658024.</ref> |
| 24 | 32 |