Orforglipron: difference between revisions
Diff·revision 8 → 9·10:32, 5 Mar 2025
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| Revision 8 — 05:17, 13 Feb 2025 LiraLotte (talk) typo 3,337 bytes ±0 | Revision 9 — 10:32, 5 Mar 2025 MassSpecMarv (talk) fix the anchor on an internal link 4,056 bytes +719 | ||
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| 1 | {{Infobox compound | 1 | {{Infobox compound |
| 2 | | name = Orforglipron | 2 | | name = Orforglipron |
| + | 3 | | subtitle = Investigational | |
| 3 | | Development code = LY3502970 | 4 | | Development code = LY3502970 |
| 4 | | Class = Small-molecule [[GLP-1 receptor agonist]] | 5 | | Class = Small-molecule [[GLP-1 receptor agonist]] |
| ⋮ | ⋮ | ||
| 24 | Signalling profile differs from that of the peptide agonists, with a reported preference for cAMP accumulation over β-arrestin recruitment. Whether that difference has clinical consequences is unknown; see [[Receptor bias]].{{r|kawai2020}} | 25 | Signalling profile differs from that of the peptide agonists, with a reported preference for cAMP accumulation over β-arrestin recruitment. Whether that difference has clinical consequences is unknown; see [[Receptor bias]].{{r|kawai2020}} |
| 25 | 26 | ||
| + | 27 | == Reported clinical findings == | |
| + | 28 | | Trial setting | Duration | Reported result | | |
| + | 29 | |---|---|---| | |
| + | 30 | | Type 2 diabetes, phase 2 | 26 weeks | HbA1c −2.1 percentage points at highest dose | | |
| + | 31 | | Obesity without diabetes, phase 2 | 36 weeks | −14.7% weight at highest dose vs −2.3% placebo | | |
| + | 32 | ||
| + | 33 | Gastrointestinal adverse events were dose-related and qualitatively similar to those of injected agonists, which argues that they are a receptor-level rather than a route-level phenomenon.{{r|frias2023orfo,drucker2018}} | |
| + | 34 | ||
| 26 | == References == | 35 | == References == |
| 27 | {{reflist}} | 36 | {{reflist}} |
| 28 | <ref name="kawai2020">Kawai T, Sun B, Yoshino H, et al. "Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist." ''Proceedings of the National Academy of Sciences'' 117(47):29959–29967 (2020). DOI:10.1073/pnas.2014879117. PMID 33177239.</ref> | 37 | <ref name="kawai2020">Kawai T, Sun B, Yoshino H, et al. "Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist." ''Proceedings of the National Academy of Sciences'' 117(47):29959–29967 (2020). DOI:10.1073/pnas.2014879117. PMID 33177239.</ref> |
| 29 | <ref name="frias2023orfo">Frías JP, Hsia S, Eyde S, et al. "Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a phase 2 randomised trial." ''The Lancet'' 402(10400):472–483 (2023). PMID 37369232.</ref> | 38 | <ref name="frias2023orfo">Frías JP, Hsia S, Eyde S, et al. "Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a phase 2 randomised trial." ''The Lancet'' 402(10400):472–483 (2023). PMID 37369232.</ref> |
| + | 39 | <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> | |
| 30 | <ref name="graaf2016">de Graaf C, Donnelly D, Wootten D, et al. "Glucagon-like peptide-1 and its class B G protein-coupled receptors." ''Pharmacological Reviews'' 68(4):954–1013 (2016). PMID 27630114.</ref> | 40 | <ref name="graaf2016">de Graaf C, Donnelly D, Wootten D, et al. "Glucagon-like peptide-1 and its class B G protein-coupled receptors." ''Pharmacological Reviews'' 68(4):954–1013 (2016). PMID 27630114.</ref> |
| 31 | 41 |