Survodutide: difference between revisions
Diff·revision 2 → 3·11:56, 20 Nov 2024
Difference between revision 2 and revision 3 of Survodutide. 6 lines changed; the page grew by 1,058 bytes.
| Revision 2 — 09:58, 10 Nov 2024 NauseaNoor (talk) ce per PP:MOS 1,456 bytes ±0 | Revision 3 — 11:56, 20 Nov 2024 IcodecIndra (talk) state the substitution in one-letter code as well, per PP:MOS 2,514 bytes +1,058 | ||
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| 11 | Unlike the GIP/GLP-1 pairing of [[Tirzepatide|tirzepatide]], the glucagon/GLP-1 pairing sets two opposing glycaemic effects against each other deliberately. Glucagon-receptor agonism raises hepatic glucose output and energy expenditure; [[GLP-1 receptor agonist|GLP-1 agonism]] lowers glucose and food intake. The design intent is to capture the energy-expenditure and hepatic-fat effects of the former while the latter dominates the net glycaemic balance.{{r|zimmermann2022}} | 11 | Unlike the GIP/GLP-1 pairing of [[Tirzepatide|tirzepatide]], the glucagon/GLP-1 pairing sets two opposing glycaemic effects against each other deliberately. Glucagon-receptor agonism raises hepatic glucose output and energy expenditure; [[GLP-1 receptor agonist|GLP-1 agonism]] lowers glucose and food intake. The design intent is to capture the energy-expenditure and hepatic-fat effects of the former while the latter dominates the net glycaemic balance.{{r|zimmermann2022}} |
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| + | 13 | == Design and rationale == | |
| + | 14 | Survodutide is a 29-residue acylated peptide derived from the glucagon sequence, with substitutions conferring GLP-1-receptor activity and a fatty-acid chain for [[Albumin binding half-life extension|albumin binding]]. Its natural template is oxyntomodulin, a product of [[Proglucagon|proglucagon]] processing that is a weak agonist at both receptors — the existence of which is why the combination was thought physiologically coherent rather than merely chemically possible.{{r|zimmermann2022,campbell2013}} | |
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| + | 16 | The potency ratio is the central design variable. Too much glucagon activity relative to GLP-1 activity raises fasting glucose; too little forfeits the energy-expenditure benefit that motivated the design. This is a fixed intramolecular property, so the balance must hold across the whole dose range rather than at one point in it. | |
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| 13 | == References == | 18 | == References == |
| 14 | {{reflist}} | 19 | {{reflist}} |
| 15 | <ref name="zimmermann2022">Zimmermann T, Thomas L, Baader-Pagler T, et al. "BI 456906: discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy." ''Molecular Metabolism'' 66:101633 (2022). DOI:10.1016/j.molmet.2022.101633. PMID 36372428.</ref> | 20 | <ref name="zimmermann2022">Zimmermann T, Thomas L, Baader-Pagler T, et al. "BI 456906: discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy." ''Molecular Metabolism'' 66:101633 (2022). DOI:10.1016/j.molmet.2022.101633. PMID 36372428.</ref> |
| + | 21 | <ref name="campbell2013">Campbell JE, Drucker DJ. "Pharmacology, physiology, and mechanisms of incretin hormone action." ''Cell Metabolism'' 17(6):819–837 (2013). PMID 23684623.</ref> | |
| 16 | 22 | ||
| 17 | {{DEFAULTSORT:Survodutide}} | 23 | {{DEFAULTSORT:Survodutide}} |