Semaglutide — reference

Semaglutide: glp-1 receptor agonist, approximate mass 4113.6 Da, 165–184 h (about one week) half-life. Identity, evidence base, analytical considerations and limitations.

Scope

A maintained identity and evidence reference for 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

Semaglutide is an acylated analogue of human GLP-1 with two substitutions and a C18 fatty diacid side chain attached via a spacer. The side chain drives reversible albumin binding, which is the single structural feature responsible for the week-long half-life; without it the molecule would behave like native GLP-1 and last minutes.

It has the largest published human dataset of any compound in this class, spanning glycaemic control, weight, cardiovascular outcomes in people with and without diabetes, renal outcomes in chronic kidney disease, and heart failure with preserved ejection fraction. That breadth is why it is the reference point against which everything else here gets compared.

Evidence base

Published studies and programmes most relevant to this compound:

• STEP 1
• STEP 2
• STEP 4
• STEP 8
• SUSTAIN 6
• SELECT
• FLOW
• PIONEER 6
• SOUL

The dose ranges studied differ substantially by indication, and dose numbers are not transferable between indications or between formulations. An oral dose and a subcutaneous dose of the same nominal size are not comparable exposures.

Gastrointestinal effects dominate the adverse-effect profile and are dose- and escalation-rate-dependent. In the trial programmes they were most prominent during titration and attenuated at a stable dose, which is consistent with what members report here.

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

Reversed-phase HPLC with ultraviolet detection at 214 nm is the usual purity method, and electrospray mass spectrometry the usual identity method. 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 and, at higher dose, for weight management in many 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.