[Discussion] non-peptide agonism is a genuinely different engineering problem
non-peptide agonism is a genuinely different engineering problem. I have gone back and forth on this for months.
Read both programme names carefully after mixing them up in a comment and being politely corrected.
Nothing containing this compound is approved by any regulator, and research-use-only material is not approved for human use.
Assumed the peptide purity conversations transferred and they do not. Different analytical problem entirely.
I will update this if the picture changes rather than quietly leaving it up.
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.
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.
Push back: daily dosing is not automatically better adherence. It is a different failure mode, not a solved problem.
ATTAIN and ACHIEVE are the programmes to keep straight
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 and non-peptide is the whole engineering story
The no-timing-restriction thing is the part I would care about most in practice, and it barely gets mentioned here.
Small fix — the two programme names got swapped upthread and it changes which population the figure came from.
daily dosing, not weekly, so the exposure profile is different
oral and non-peptide is the whole engineering story
Agreed, and it is why the oral peptide comparison keeps misleading people.
Milligram-for-milligram comparison with an injectable peptide is not meaningful and I should not have made it.
Which programme and which readout are you quoting?
Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.
Corrected a cross-class dose comparison in the title. The body is untouched.
Right, and comparing milligrams between a small molecule and a peptide is meaningless in either direction.
What did the tolerability table look like at that dose?
Went looking for independent testing on this and found essentially nothing, which was clarifying.
- 1ATTAIN and ACHIEVE are the programmes to keep straight14 comments in this branch · started by u/hamza_weiss