reading ATTAIN threads from 2024 and half of it aged badly
Posting this as a discussion rather than a claim: reading ATTAIN threads from 2024 and half of it aged badly.
Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
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.
Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.
best — the order this archive was captured in
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.
Standing reminder: unapproved compound, research material is not for human use, and no schedules for other members.
Phase 2 or phase 3?
Milligram-for-milligram comparison with an injectable peptide is not meaningful and I should not have made it.
the tolerability profile reads broadly similar to the class
Standing reminder: unapproved compound, research material is not for human use, and no schedules for other members.
trialwatch_theo is right that milligram comparisons across classes tell you nothing.
do not assume reconstitution intuitions apply, there is nothing to reconstitute
do not assume reconstitution intuitions apply, there is nothing to reconstitute
Agreed, and it is why the oral peptide comparison keeps misleading people.
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.
This. The absence of food and water timing restrictions is the practical difference people will actually notice.
Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.
Which programme and which readout are you quoting?
Went looking for independent testing on this and found essentially nothing, which was clarifying.
Why "oral" is doing two completely different jobs in the sentences people write here.
Oral semaglutide is a peptide co-formulated with an absorption enhancer, which is why it comes with food and water timing requirements. This compound is a non-peptide small molecule that activates the same receptor, formulated as an ordinary tablet.
The practical consequences differ enormously: no timing constraints, a conventional manufacturing route, different stability behaviour, and a different analytical problem for anybody trying to verify identity or purity. Whenever a thread here compares the two, check which sense of "oral" each half is using.
Why "oral" is doing two completely different jobs in the sentences people write here.
This is the fact the whole board hangs on. Small molecule, not peptide.
The analytical point, which this board keeps getting wrong by importing habits from the peptide side.
For a peptide, purity is typically reported as area percent by HPLC with identity by mass spectrometry, and the impurity classes are things like deletion and oxidation products. For a small molecule the relevant impurities are synthetic intermediates, degradants and residual solvents, and identity is established differently.
So the certificate you would want looks different, the questions to ask are different, and a "purity" figure quoted here is not comparable to one quoted on the peptide boards. Anybody posting a result should say what method produced it, which is good practice everywhere and essential here.
the boards keep comparing it to injectables at matched doses, which is meaningless
Has anyone here seen independent identity testing on this?
the boards keep comparing it to injectables at matched doses, which is meaningless
Disagreeing with this bit: daily dosing is a different adherence problem, not a better one.
Daily dosing, so what does the exposure profile look like across the day?
phase 3 is where the comparison becomes fair
oral semaglutide is a peptide with an absorption enhancer, this is not that
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Agreed that phase 3 is where the comparison becomes fair. Everything before it is inference.
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