genuine question about oral GLP-1 that I am slightly embarrassed to ask
genuine question about oral GLP-1 that I am slightly embarrassed to ask. I am not trying to be the "source?" guy. I would just like a source.
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.
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.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
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.
Spent an evening reading about small-molecule agonism at a peptide receptor. Genuinely interesting engineering.
Are you comparing doses across a small molecule and a peptide?
do not assume reconstitution intuitions apply, there is nothing to reconstitute
Nothing containing this compound is approved by any regulator, and research-use-only material is not approved for human use.
Small fix — the two programme names got swapped upthread and it changes which population the figure came from.
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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.
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.
Agreed — non-peptide is the fact that everything else follows from, including the manufacturing and the analytics.
the tolerability profile reads broadly similar to the class
Milligram-for-milligram comparison with an injectable peptide is not meaningful and I should not have made it.
This. The absence of food and water timing restrictions is the practical difference people will actually notice.
small molecule, not a peptide, and that changes everything about it
Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.
phase 3 is where the comparison becomes fair
Careful — purity methods for peptides do not read across to a small molecule and the numbers are not equivalent.
Assumed the peptide purity conversations transferred and they do not. Different analytical problem entirely.
identity testing on a small molecule is a different analytical problem
the manufacturing story is genuinely different from the injectables
What analytical method was used — this is not the usual peptide assay question?
Has anyone here seen independent identity testing on this?
the manufacturing story is genuinely different from the injectables
This is the fact the whole board hangs on. Small molecule, not peptide.
- 1It is a non-peptide small-molecule agonist at the GLP-1 receptor. That is a…8 comments in this branch · started by u/bruno_dumitru
- 2Are you comparing doses across a small molecule and a peptide?6 comments in this branch · started by u/lina_novak