Liraglutide: difference between revisions
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| Revision 1 — 09:00, 12 Aug 2024 Peptide_Pete (talk) create article — compound stub 1,442 bytes +1,442 | Revision 2 — 01:12, 16 Aug 2024 SemaglutideSasha (talk) the storage condition applies to the unopened pen; say so 2,493 bytes +1,051 | ||
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| 11 | The resulting half-life of about thirteen hours supports once-daily subcutaneous dosing. Liraglutide was approved for type 2 diabetes in 2009 and, at a higher dose, for weight management in 2014; the LEADER trial subsequently established cardiovascular benefit in type 2 diabetes with high cardiovascular risk.{{r|marso2016}} | 11 | The resulting half-life of about thirteen hours supports once-daily subcutaneous dosing. Liraglutide was approved for type 2 diabetes in 2009 and, at a higher dose, for weight management in 2014; the LEADER trial subsequently established cardiovascular benefit in type 2 diabetes with high cardiovascular risk.{{r|marso2016}} |
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| + | 13 | == Chemistry == | |
| + | 14 | Liraglutide differs from native GLP-1(7–37) in two respects: Lys34 is replaced by arginine, and a palmitoyl group is attached to Lys26 through a γ-glutamate linker. The peptide backbone otherwise retains the native sequence, including the alanine at position 8 that [[Dipeptidyl peptidase-4|DPP-4]] cleaves.{{r|knudsen2019}} | |
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| + | 16 | That last point is important and is often misstated. Liraglutide is not DPP-4 resistant by substitution; its resistance is conferred indirectly, because the albumin-bound fraction is sterically inaccessible to the protease and only the small free fraction is exposed. The molecule also self-associates into heptamers in the pharmaceutical formulation, which slows absorption from the subcutaneous depot and contributes as much to the duration of action as albumin binding does.{{r|lau2015}} | |
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| 13 | == References == | 18 | == References == |
| 14 | {{reflist}} | 19 | {{reflist}} |
| 15 | <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> | 20 | <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> |
| + | 21 | <ref name="lau2015">Lau J, Bloch P, Schäffer L, et al. "Discovery of the once-weekly glucagon-like peptide-1 analog semaglutide." ''Journal of Medicinal Chemistry'' 58(18):7370–7380 (2015). PMID 26308095.</ref> | |
| 16 | <ref name="marso2016">Marso SP, Daniels GH, Brown-Frandsen K, et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." ''New England Journal of Medicine'' 375(4):311–322 (2016). DOI:10.1056/NEJMoa1603827. PMID 27295427.</ref> | 22 | <ref name="marso2016">Marso SP, Daniels GH, Brown-Frandsen K, et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." ''New England Journal of Medicine'' 375(4):311–322 (2016). DOI:10.1056/NEJMoa1603827. PMID 27295427.</ref> |
| 17 | 23 |