three years of oral GLP-1 threads, summarised so you do not have to read them
three years of oral GLP-1 threads, summarised so you do not have to read them. Change my mind, genuinely — I have no stake in being right about this.
Analytically this is a small-molecule identity and purity problem, not a peptide one. The methods, the impurity classes and the reference standards are all different.
Oral semaglutide is a peptide co-formulated with an absorption enhancer and carries food and water timing requirements. A small molecule does not have that constraint, which is the practical distinction.
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
If two or three other people have done the same thing we might actually learn something. Alone it is an anecdote.
best — the order this archive was captured in
Nothing containing this compound is approved by any regulator, and research-use-only material is not approved for human use.
Careful — purity methods for peptides do not read across to a small molecule and the numbers are not equivalent.
Because it is not a peptide, it is not subject to the same degradation pathways, does not require the absorption enhancers used for oral peptides, and can be formulated as a conventional tablet.
Because it is not a peptide, it is not subject to the same degradation pathways, does not require the absorption enhancers used for oral peptides, and
ines_lindqvist is right that milligram comparisons across classes tell you nothing.
It is a non-peptide small-molecule agonist at the GLP-1 receptor. That is a substantial medicinal chemistry achievement: getting a small molecule to activate a receptor evolved for a peptide ligand.
Daily dosing, so what does the exposure profile look like across the day?
Milligram-for-milligram comparison with an injectable peptide is not meaningful and I should not have made it.
Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.
Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.
Not convinced. Oral semaglutide is a peptide formulated with an absorption enhancer; the comparison you are making does not hold.
Not convinced.
This is the fact the whole board hangs on. Small molecule, not peptide.
This is the fact the whole board hangs on.
Agreed, and it is why the oral peptide comparison keeps misleading people.
Are you comparing doses across a small molecule and a peptide?
Small fix — the two programme names got swapped upthread and it changes which population the figure came from.
Phase 2 or phase 3?
small molecule, not a peptide, and that changes everything about it
daily dosing changes adherence in both directions
What analytical method was used — this is not the usual peptide assay question?
What analytical method was used — this is not the usual peptide assay question?
Disagreeing with this bit: daily dosing is a different adherence problem, not a better one.
I would not assume the tolerability profile transfers exactly. Similar class effects, different exposure profile.
That is a phase 2 result being quoted as though the programme had reported.
Yes — nothing containing this is approved anywhere, and the threads keep forgetting it.
Which programme and which readout are you quoting?
a non-peptide agonist does not degrade the way a peptide does
Is that from the publication or the press release?
Disagree. You are comparing doses across a small molecule and a peptide, which is not a comparison of anything.
Has anyone here seen independent identity testing on this?
The no-timing-restriction thing is the part I would care about most in practice, and it barely gets mentioned here.
Standing reminder: unapproved compound, research material is not for human use, and no schedules for other members.
- 1Not convinced. Oral semaglutide is a peptide formulated with an absorption…9 comments in this branch · started by u/nils_ferreira
- 2What analytical method was used — this is not the usual peptide assay…6 comments in this branch · started by u/cloudy_vial_carol