my TSH moved and I cannot work out whether ACHIEVE is why
my TSH moved and I cannot work out whether ACHIEVE is why — a position I have arrived at slowly and would like tested.
What is actually known, and what is being assumed.
Known: it is a small-molecule GLP-1 receptor agonist, dosed daily, with clinical programmes reporting in both obesity and type 2 diabetes. Its tolerability profile broadly resembles the class in the data published so far.
Assumed, frequently and confidently: that milligram comparisons with injectables mean something, that adherence is straightforwardly better because it is a tablet, that peptide purity discussions transfer to it. None of those hold. And nothing containing this compound is approved anywhere, which makes research-use-only material exactly that — not approved for human use.
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.
Happy to answer the boring questions. Those are usually the ones worth asking.
best — the order this archive was captured in
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.
Not convinced. Oral semaglutide is a peptide formulated with an absorption enhancer; the comparison you are making does not hold.
This. The absence of food and water timing restrictions is the practical difference people will actually notice.
oral semaglutide is a peptide with an absorption enhancer, this is not that
Holding off on any opinion until phase 3 reports. That is not a satisfying position and it is the honest one.
Right, and comparing milligrams between a small molecule and a peptide is meaningless in either direction.
Went looking for independent testing on this and found essentially nothing, which was clarifying.
Standing reminder: unapproved compound, research material is not for human use, and no schedules for other members.
Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.
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What did the tolerability table look like at that dose?
a non-peptide agonist does not degrade the way a peptide does
That is a phase 2 result being quoted as though the programme had reported.
daily dosing changes adherence in both directions
Cosigning on daily dosing. It changes the exposure profile and it changes adherence, in both directions.
Agreed that phase 3 is where the comparison becomes fair. Everything before it is inference.
ATTAIN and ACHIEVE are the programmes to keep straight
The no-timing-restriction thing is the part I would care about most in practice, and it barely gets mentioned here.
The no-timing-restriction thing is the part I would care about most in practice, and it barely gets mentioned here.
Disagreeing with this bit: daily dosing is a different adherence problem, not a better one.
Daily rather than weekly sounds trivial until you think about what a missed dose means in each case.
Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.
Disagree. You are comparing doses across a small molecule and a peptide, which is not a comparison of anything.
Which programme and which readout are you quoting?
the manufacturing story is genuinely different from the injectables
- 1Agreed that phase 3 is where the comparison becomes fair. Everything before…9 comments in this branch · started by u/deleted_my_history
- 2Standing reminder: unapproved compound, research material is not for human…8 comments in this branch · started by u/incretin_ivy