Oral semaglutide — reference

Oral semaglutide: glp-1 receptor agonist, oral formulation, approximate mass 4113.6 Da (same molecule), 1 week half-life. Identity, evidence base, analytical considerations and limitations.

Scope

A maintained identity and evidence reference for Oral semaglutide. It is deliberately narrow: what the molecule is, what has been published about it, and what an analytical report on it can and cannot establish. It contains no dosing recommendations and is not advice about anyone's care.

Where a figure is approximate this page says so. Where something is unknown, it says that instead of filling the gap.

Identity

Masses quoted here are approximate and are given for orientation when reading an analytical report. For a mass-error calculation, use the exact monoisotopic mass computed from the elemental composition rather than a rounded figure from a reference page, including this one.

What it is

The molecule is identical to injectable semaglutide. What differs is the tablet, which co-formulates the peptide with sodium N-(8-[2-hydroxybenzoyl]amino) caprylate, usually called SNAC. SNAC transiently raises local pH in the stomach and promotes absorption across the gastric mucosa.

Oral bioavailability is low and variable, which is why the oral dose numbers are an order of magnitude larger than the injectable ones. Comparing the two by dose is meaningless.

Evidence base

Published studies and programmes most relevant to this compound:

• PIONEER 1
• PIONEER 6
• SOUL
• OASIS programme

The administration instructions are not lifestyle advice: taking the tablet with food or with a substantial volume of water measurably reduces absorption. This is the one compound in this class where the instructions genuinely determine the exposure.

SOUL is the cardiovascular outcome trial for the oral formulation and PIONEER 6 was the earlier cardiovascular safety trial.

Individual digests for several of these are maintained separately in this commons and are linked from the evidence category. A digest is a summary with its criticisms attached; it is not a substitute for reading the paper.

Analytical considerations

The usual analytical approach depends on whether the molecule is a peptide; where it is not, peptide conventions do not transfer. A purity figure is an area percentage at a stated wavelength under a stated gradient, and it is not interchangeable with a content determination.

Three things a purity assay on this compound will not tell you: how much peptide is in the container (that requires a content assay), what the counter-ion is (that requires ion chromatography or NMR), and whether anything is present that does not elute under the method used.

See Reversed-phase HPLC for peptides and LC-MS identity confirmation for the method detail.

Status and legality

Licensed for type 2 diabetes; higher-dose obesity formulations under review in some jurisdictions.

Material sold as research-use-only is not a licensed medicine, whatever it contains and however good its certificate is. That is a statement about regulatory status rather than about quality, and it is true of high-purity material as much as of poor material.

Limitations of this page

This is a reference page maintained by volunteers, reviewed on the date shown, and it will be out of date at some point after that date. It summarises published work rather than reproducing it, and a summary always loses something. Where the summary and the source disagree, the source is right.

If you find an error, the fastest route to fixing it is a topic in doc review naming the sentence and the source. The maintainers named above are notified.