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Semaglutide: difference between revisions

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11It is approved for type 2 diabetes, for chronic weight management, and — following the [[SELECT trial|SELECT]] trial — for reduction of major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity but without diabetes. An oral formulation using the absorption enhancer SNAC is approved for type 2 diabetes.{{r|lincoff2023}}11It is approved for type 2 diabetes, for chronic weight management, and — following the [[SELECT trial|SELECT]] trial — for reduction of major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity but without diabetes. An oral formulation using the absorption enhancer SNAC is approved for type 2 diabetes.{{r|lincoff2023}}
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+13In the [[STEP trial programme|STEP 1]] trial, weekly semaglutide 2.4 mg produced a mean body-weight change of −14.9% against −2.4% for placebo at 68 weeks.{{r|wilding2021}} Semaglutide is also among the most heavily copied peptides in the research-chemical market, and material sold that way is not the approved medicine: it is not manufactured under a marketing authorisation and carries no regulatory assurance of identity, purity, sterility or fill mass. See [[Research use only]].
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13== Chemistry and engineering ==15== Chemistry and engineering ==
14The native GLP-1(7–37) backbone was modified at three positions. The alanine at position 8 — the second residue of the mature hormone and the site of [[Dipeptidyl peptidase-4|DPP-4]] cleavage — was replaced with α-aminoisobutyric acid, a non-proteinogenic residue whose gem-dimethyl substitution prevents the protease from engaging the peptide.{{r|lau2015}}16The native GLP-1(7–37) backbone was modified at three positions. The alanine at position 8 — the second residue of the mature hormone and the site of [[Dipeptidyl peptidase-4|DPP-4]] cleavage — was replaced with α-aminoisobutyric acid, a non-proteinogenic residue whose gem-dimethyl substitution prevents the protease from engaging the peptide.{{r|lau2015}}
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22<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). DOI:10.1021/acs.jmedchem.5b00726. PMID 26308095.</ref>24<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). DOI:10.1021/acs.jmedchem.5b00726. PMID 26308095.</ref>
23<ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref>25<ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref>
+26<ref name="wilding2021">Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." ''New England Journal of Medicine'' 384(11):989–1002 (2021). DOI:10.1056/NEJMoa2032183. PMID 33567185.</ref>
24<ref name="lincoff2023">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." ''New England Journal of Medicine'' 389(24):2221–2232 (2023). PMID 37952131.</ref>27<ref name="lincoff2023">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." ''New England Journal of Medicine'' 389(24):2221–2232 (2023). PMID 37952131.</ref>
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