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

[Lab] QYB orfo — Medutest came back 99.3% against a claimed 99.0%

Trial Data Well Actually ×1

Short version of the title, which is already short: QYB orfo — Medutest came back 99.3% against a claimed 99.0%. Longer version underneath.

Numbers, in the order they matter: 99.3% and 99.0%.

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.

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.

Ask me anything specific. Anything general I will probably get wrong.

858 up / 164 down84% upvoted31 commentsid zlia7f8 Mar 2024
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31 comments

23 in this archive, depth 6

best — the order this archive was captured in

u/clara_weiss71 points·2 years ago·edited

Nothing containing this compound is approved by any regulator, and research-use-only material is not approved for human use.

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u/clara_weiss21 points·2 years ago

Which programme and which readout are you quoting?

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[deleted]8 points·2 years ago

[deleted]

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u/sanne_delgado17 points·2 years ago

Which programme and which readout are you quoting?

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

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u/joaquin_trevino42 points·2 years ago

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.

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u/phase_two_peteMOD32 points·2 years ago

Left up. It is careful about what is peptide and what is not, which is more than most threads here manage.

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u/ravi_sandvikOP24 points·2 years ago

Is that from the publication or the press release?

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u/maren_sorensen25 points·2 years ago

Small fix — the two programme names got swapped upthread and it changes which population the figure came from.

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u/ravi_sandvikOP10 points·2 years ago

Milligram-for-milligram comparison with an injectable peptide is not meaningful and I should not have made it.

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u/chidi_yilmaz0 points·2 years ago

Small fix — the two programme names got swapped upthread and it changes which population the figure came from.

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

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u/certified_referenceQC27 points·2 years ago

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

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u/camila_vasquez32 points·2 years ago·edited

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

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u/ravi_sandvikOP14 points·2 years ago

identity testing on a small molecule is a different analytical problem

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u/marit_laurent-11 points·2 years ago

Holding off on any opinion until phase 3 reports. That is not a satisfying position and it is the honest one.

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u/yannick_salinas11 points·2 years ago

I would not assume the tolerability profile transfers exactly. Similar class effects, different exposure profile.

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u/lukas_delgado5 points·2 years ago

nothing containing this is approved anywhere yet

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u/gustav_solberg5 points·2 years ago

Agreed — non-peptide is the fact that everything else follows from, including the manufacturing and the analytics.

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u/hedda_ekstrom1 point·2 years ago

oral and non-peptide is the whole engineering story

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u/marit_laurent15 points·2 years ago

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

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u/ice_pack_auditcold chain18 points·2 years ago

Daily dosing, so what does the exposure profile look like across the day?

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u/scam_taxonomyc/scamalerts14 points·2 years ago

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.

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u/lukas_delgado11 points·2 years ago

the boards keep comparing it to injectables at matched doses, which is meaningless

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u/zeynep_ndiaye7 points·2 years ago

What analytical method was used — this is not the usual peptide assay question?

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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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