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c/orforglipron·posted 5 months ago by u/canada_coverage

8 months in and orforglipron is still the thing I get wrong

Discussion Long Haul ×6

8 months in and orforglipron is still the thing I get wrong, logged the same way every week so the comparison is at least internally fair.

The relevant figures are 8 months, and they come from the same log I have kept the whole time.

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.

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.

Research-use-only material is not approved for human use and nothing here should be read as a recommendation to use it.

3,491 up / 3,115 down53% upvoted23 commentsid w029sg26 Feb 2026

23 comments

17 in this archive, depth 3

best — the order this archive was captured in

u/clara_weiss-8 points·5 months 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/trialwatch_theotrial nerd1 point·5 months ago

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

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u/quiet_moderatormod1 point·5 months ago

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

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u/joaquin_trevino23 points·5 months ago

Yes — nothing containing this is approved anywhere, and the threads keep forgetting it.

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[deleted]9 points·5 months ago

[deleted]

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u/anders_karlsen6 points·5 months 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/canada_coverageOP18 points·5 months ago

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

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u/cato_batista18 points·5 months ago

the manufacturing story is genuinely different from the injectables

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u/farid_kuipers10 points·5 months ago·edited

the manufacturing story is genuinely different from the injectables

Agreed, and it is why the oral peptide comparison keeps misleading people.

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u/adaeze_cabrera4 points·5 months 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/canada_coverageOP2 points·5 months ago

What did the tolerability table look like at that dose?

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u/neha_rahimi4 points·5 months ago

daily dosing changes adherence in both directions

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u/pancreatitis_scare3 points·5 months ago

Is that from the publication or the press release?

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u/gustav_solberg11 points·5 months ago

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

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u/anders_karlsen7 points·5 months ago·edited

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

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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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