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c/orforglipron·posted 1 year ago by u/tobias_molnar

unpopular opinion: most of what gets said here about orforglipron is guesswork

Paper

unpopular opinion: most of what gets said here about orforglipron is guesswork. Making the case below, and I expect to lose some of it in the comments.

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.

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.

Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.

576 up / 599 down50% upvoted11 commentsid 1r3a6j3 Feb 2025

11 comments

11 in this archive, depth 5

best — the order this archive was captured in

u/yara_boateng10 points·1 year ago

Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.

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u/emeka_delgado8 points·1 year ago

Daily dosing gives a very different exposure profile from a weekly injectable: peaks and troughs within each day rather than a smoothed weekly curve.

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

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[removed]7 points·1 year ago

[removed by moderator]

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u/kavya_radich6 points·1 year ago

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/greta_nilsen2 points·1 year 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/erez_yilmaz3 points·1 year ago

Milligram comparisons across molecule classes are meaningless. Potency is a property of the molecule at its receptor, not of the number on the label.

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u/tobias_molnarOP2 points·1 year ago

Correcting myself: that was a phase 2 readout and I described it as phase 3.

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u/discount_math_dm1 point·1 year ago

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

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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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