Source of Oral semaglutide

{{Infobox compound | name = Oral semaglutide | subtitle = Formulation | Active = [[Semaglutide|Semaglutide]] | Enhancer = Sodium N-(8-(2-hydroxybenzoyl)amino)caprylate | Bioavailability = ≈0.4–1% | Conditions = Fasting, ≤120 mL water, 30-minute wait }} '''Oral semaglutide''' is a tablet formulation of [[Semaglutide|semaglutide]] co-formulated with the absorption enhancer sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, generally abbreviated SNAC. It was the first orally administered [[GLP-1 receptor agonist]] to be approved.{{r|knudsen2019}} Peptides are not orally bioavailable: gastric acid and proteases degrade them, and the intestinal epithelium excludes molecules of that size. SNAC addresses both by buffering the local gastric pH and transiently increasing local permeability, allowing absorption across the gastric mucosa itself rather than in the intestine.{{r|buckley2018}} The resulting bioavailability is roughly 0.4–1%, which is why the oral dose is an order of magnitude larger than the injected one in milligram terms. It is also critically dependent on dosing conditions.{{r|buckley2018}} == The absorption mechanism == SNAC acts locally and transiently. It raises pH in the immediate vicinity of the dissolving tablet, protecting the peptide from pepsin, and promotes transcellular absorption across the gastric epithelium. The effect is confined to the region around the tablet and to the period during which it dissolves.{{r|buckley2018}} Because absorption occurs at the tablet's location, anything that moves the tablet or dilutes the local environment reduces exposure. This is why the dosing conditions — fasting, no more than 120 mL of water, and a further 30 minutes without food, drink or other oral medicines — are part of the product rather than advice.{{r|knudsen2019}} Deviations change exposure severalfold, and between-individual variability is correspondingly larger than for the injected formulation.{{r|buckley2018}} == Clinical position == Approved for type 2 diabetes, oral semaglutide reduces glycated haemoglobin by roughly 1.0–1.4 percentage points at the studied doses, with modest weight reduction — smaller effects than weekly injected semaglutide at its obesity dose.{{r|knudsen2019}} Its advantage is route. For someone unwilling or unable to inject, an oral option changes what treatment is available at all, and this is the axis on which it competes rather than on effect size.{{r|drucker2018}} The small-molecule agonists such as [[Orforglipron|orforglipron]] address the same problem differently: not being peptides, they need neither an enhancer nor fasting conditions.{{r|drucker2018}} == Analytical and handling notes == A tablet is a different analytical object from a lyophilised powder. Content uniformity, dissolution and the enhancer's own assay are part of its specification, none of which appears on a peptide [[Certificate of analysis|certificate of analysis]].{{r|usp1503}} Research-chemical supply of this formulation is uncommon, since a co-formulated tablet is a manufactured drug product rather than a bulk peptide, and reproducing it is a formulation exercise rather than a synthesis.{{r|reports}} Material sold as "oral semaglutide" in powder or capsule form outside licensed supply is not this product, whatever its peptide content, because the enhancer and the tablet architecture are what produce the absorption.{{r|usp1503}} == References == {{reflist}} <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> <ref name="buckley2018">Buckley ST, Bækdal TA, Vegge A, et al. "Transcellular stomach absorption of a derivatised glucagon-like peptide-1 receptor agonist." ''Science Translational Medicine'' 10(467):eaar7047 (2018). PMID 30429357.</ref> <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> <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> <ref name="reports">PeptidePedia Wiki community test-report tally, 2024–2026 (self-reported; see [[Project:Sourcing_guidelines]]).</ref> == See also == * [[Semaglutide]] * [[Orforglipron]] * [[GLP-1 receptor agonist]] * [[Gastric emptying]] {{DEFAULTSORT:Oral semaglutide}} [[Category:GLP-1 receptor agonists]] [[Category:Peptide drugs]] [[Category:Pharmacokinetics]]