Semaglutide, oral — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Semaglutide, oral, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GLP-1 receptor (GLP1R) | Full agonist | Identical receptor pharmacology to the subcutaneous product |
| SNAC-mediated gastric absorption | Excipient mechanism | Localised, saturable, and highly sensitive to concomitant fluid and food |
§2.2Mechanism of action
Receptor pharmacology is identical to subcutaneous semaglutide. The distinguishing pharmacology is absorption: SNAC buffers the gastric microenvironment, inhibits local pepsin activity and transiently increases permeability, producing absolute bioavailability of approximately 0.4–1.0 %. Absorption occurs over a narrow gastric window, which makes exposure unusually sensitive to dosing conditions and explains the strict administration instructions.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈160 h (approximately 7 days), matching the subcutaneous product
- Time to maximum concentration
- ≈1 h post-dose for the absorption peak
- Volume of distribution
- ≈8 L (apparent)
- Plasma protein binding
- >99 % (albumin)
- Clearance
- ≈0.04 L/h
- Bioavailability
- 0.4–1.0 % absolute
Identical metabolic fate to subcutaneous semaglutide. Between-subject exposure variability is substantially higher than for the injectable product, with coefficients of variation reported above 100 % in some analyses.
§2.4Interactions
- Levothyroxine — increased exposure; monitor thyroid function
- Any oral medicine taken within 30 minutes may have altered absorption
- Omeprazole did not meaningfully change semaglutide exposure in dedicated study
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, Jeppesen OK, Lingvay I, Mosenzon O, Pedersen SD, Tack CJ, Thomsen M, Vilsbøll T, Warren ML, Bain SC. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 2019;381(9):841–851. doi:10.1056/NEJMoa1901118 · PMID 31185157
- Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzík M. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019;42(9):1724–1732. doi:10.2337/dc19-0749 · PMID 31186300
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.