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c/orforglipron·posted 2 years ago by u/bruno_dumitru

[Question] small molecule — what am I missing here

Question Slow Clap ×2 Receipts ×1

small molecule — what am I missing here. Searched first, found three threads that contradict each other, hence the post.

Compared milligram figures across two completely different molecule classes in a comment. Deserved the correction.

Went looking for independent testing on this and found essentially nothing, which was clarifying.

Daily rather than weekly sounds trivial until you think about what a missed dose means in each case.

Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.

1,372 up / 361 down79% upvoted67 commentsid 1wwg1y19 Apr 2024

67 comments

28 in this archive, depth 4

best — the order this archive was captured in

u/pancreatitis_scare129 points·2 years ago

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.

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u/greta_nilsen44 points·2 years ago

Read both programme names carefully after mixing them up in a comment and being politely corrected.

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[deleted]49 points·2 years ago

[deleted]

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u/erez_yilmaz40 points·2 years ago

oral semaglutide is a peptide with an absorption enhancer, this is not that

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u/dilara_weiss20 points·2 years ago

do not assume reconstitution intuitions apply, there is nothing to reconstitute

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u/maren_sorensen22 points·2 years ago

Disagree. You are comparing doses across a small molecule and a peptide, which is not a comparison of anything.

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u/freya_marchand-11 points·2 years ago

That is a phase 2 result being quoted as though the programme had reported.

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u/sanne_delgado1 point·2 years ago

That is a phase 2 result being quoted as though the programme had reported.

Adding the standing caveat — unapproved, and research material is not for human use.

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u/certified_referenceQC1 point·2 years ago

oral and non-peptide is the whole engineering story

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u/chidi_yilmaz-17 points·2 years ago

the tolerability profile reads broadly similar to the class

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u/mateusz_mensah1 point·2 years ago

the tolerability profile reads broadly similar to the class

chidi_yilmaz is right that milligram comparisons across classes tell you nothing.

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u/tomas_lundgren1 point·2 years ago

The no-timing-restriction thing is the part I would care about most in practice, and it barely gets mentioned here.

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u/tidy_vialdrawer_watch281 point·2 years ago

Cosigning on daily dosing. It changes the exposure profile and it changes adherence, in both directions.

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u/tobias_molnar1 point·2 years ago

ATTAIN and ACHIEVE are the programmes to keep straight

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u/blank_injection59 points·2 years ago

Push back: daily dosing is not automatically better adherence. It is a different failure mode, not a solved problem.

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u/yara_boateng29 points·2 years ago

Push back: daily dosing is not automatically better adherence.

Disagreeing with this bit: daily dosing is a different adherence problem, not a better one.

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u/erez_yilmaz45 points·2 years ago

Yes. Oral peptide with an absorption enhancer and oral small molecule are completely different propositions.

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u/salma_almeida29 points·2 years ago

Careful — purity methods for peptides do not read across to a small molecule and the numbers are not equivalent.

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u/bruno_dumitru26 points·2 years ago

Not convinced. Oral semaglutide is a peptide formulated with an absorption enhancer; the comparison you are making does not hold.

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u/tidy_vialdrawer_watch2821 points·2 years ago

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.

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u/canada_coverage20 points·2 years ago

Correction: that is the oral peptide product, which is a different thing entirely. This one is a small molecule.

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u/bruno_dumitruOP15 points·2 years ago

daily dosing, not weekly, so the exposure profile is different

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u/yannick_salinas19 points·2 years ago

nothing containing this is approved anywhere and research material is not for human use

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u/yannick_salinas13 points·2 years ago

Assumed the peptide purity conversations transferred and they do not. Different analytical problem entirely.

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u/yara_boateng8 points·2 years ago·edited

Assumed the peptide purity conversations transferred and they do not.

This is the fact the whole board hangs on. Small molecule, not peptide.

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u/flair_enthusiast13 points·2 years ago·edited

Spent an evening reading about small-molecule agonism at a peptide receptor. Genuinely interesting engineering.

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u/scam_taxonomyc/scamalerts16 points·2 years ago

no food and water restrictions is the practical difference people care about

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u/nils_ferreira9 points·2 years ago

This. The absence of food and water timing restrictions is the practical difference people will actually notice.

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About c/orforglipron

The small-molecule oral: why a non-peptide agonist escapes the absorption problems of oral semaglutide, what the ATTAIN and ACHIEVE readouts showed, and what a pill with no refrigeration requirement would do to the entire supply conversation this site is built around.

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