[Discussion] ATTAIN is doing more work than we give it credit for
Something I keep coming back to: ATTAIN is doing more work than we give it credit for.
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.
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.
Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.
Ask me anything specific. Anything general I will probably get wrong.
best — the order this archive was captured in
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.
Spent an evening reading about small-molecule agonism at a peptide receptor. Genuinely interesting engineering.
This. The absence of food and water timing restrictions is the practical difference people will actually notice.
Push back: daily dosing is not automatically better adherence. It is a different failure mode, not a solved problem.
Push back: daily dosing is not automatically better adherence.
Adding the standing caveat — unapproved, and research material is not for human use.
nothing containing this is approved anywhere and research material is not for human use
the tolerability profile reads broadly similar to the class
Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.
Careful — purity methods for peptides do not read across to a small molecule and the numbers are not equivalent.
the boards keep comparing it to injectables at matched doses, which is meaningless
Went looking for independent testing on this and found essentially nothing, which was clarifying.
nothing containing this is approved anywhere yet
small molecule, not a peptide, and that changes everything about it
What analytical method was used — this is not the usual peptide assay question?
Disagree. You are comparing doses across a small molecule and a peptide, which is not a comparison of anything.
a non-peptide agonist does not degrade the way a peptide does
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
Disagreeing with this bit: daily dosing is a different adherence problem, not a better one.
Small fix — the two programme names got swapped upthread and it changes which population the figure came from.
identity testing on a small molecule is a different analytical problem
ATTAIN and ACHIEVE are the programmes to keep straight
- 1Push back: daily dosing is not automatically better adherence. It is a…13 comments in this branch · started by u/graph_it_gary