Compounds · Oral incretins

Second pass at: Orforglipron as a non-peptide: what changes when the molecule is small

Compounds › Oral incretins PIONEER programme orforglipron randomised trial SOUL trial oral semaglutide

c.falkTL223 Jun 2026#1

Second pass at: Orforglipron as a non-peptide: what changes when the molecule is small Writing it up because I had to work it out twice and would rather nobody else did.

Posting a small dataset on Orforglipron. It is mine, it is uncontrolled, and the method is stated so it can be discounted appropriately.

What I would like is not agreement but a second dataset collected by someone with no stake in mine. If one exists I would rather read it than argue for this one.

33 likes 1mo

m.achebeTL213 Jul 2026#2

Why an oral formulation is a formulation achievement: the molecule is the same but the tablet is novel. Getting a peptide across the gastric epithelium at usable bioavailability is a chemistry problem, not a dose problem.

One more caveat and then I will stop qualifying: the sample selected itself.

7 likes 15d

s.dziedzicTL228 Jul 2026 · edited#3

The opening post and I disagree about the size of the effect, not about the direction.

Orforglipron is a small molecule, not a peptide. That changes almost everything: no absorption enhancer required, no fasting window, chemical synthesis instead of peptide synthesis, different analytical methods entirely. Data from peptide agonists does not transfer.

I keep a log of this specifically because memory is unreliable about it.

0 likes 6h

Promoted into the documentation commons. The content of this topic is maintained at Oral semaglutide — reference, with named maintainers and a review date. The promotion was discussed in doc review. Corrections are best raised against the document, which is the version that gets kept current.

Suggested topics

Topic	Participants	Replies	Views	Activity
SNAC and the mechanism of oral peptide absorption Compounds › Oral incretins orforglipron randomised trial PIONEER programme oral semaglutide On the subject in the title: SNAC and the mechanism of oral peptide absorption Working notes rather than a conclusion. A comparison question rather than a question about one compound. Two things in the same…	+13	17	14k	17mo
Dose numbers for oral formulations are not comparable to injectable ones — a second dataset Compounds › Oral incretins randomised trial orforglipron PIONEER programme Dose numbers for oral formulations are not comparable to injectable ones — a second dataset Writing it up because I had to work it out twice and would rather nobody else did. Posting a small dataset on Dose…	+48	52	59k	18mo
Orforglipron as a non-peptide: what changes when the molecule is small Compounds › Oral incretins orforglipron SOUL trial PIONEER programme On the subject in the title: Orforglipron as a non-peptide: what changes when the molecule is small Working notes rather than a conclusion. What changes if the standard account of orforglipron is wrong? I ask…	+26	30	26k	23mo
PIONEER 6 cardiovascular safety, read as a safety trial rather than an efficacy one Compounds › Oral incretins PIONEER programme SOUL trial randomised trial orforglipron Solved PIONEER 6 cardiovascular safety, read as a safety trial rather than an efficacy one — setting out what I have, and where I think it stops being reliable. Posting a small dataset on PIONEER 6 cardiovascular…	+25	29	22k	1d
Why an oral GLP-1 agonist is a formulation achievement more than a chemistry one Compounds › Oral incretins oral semaglutide randomised trial PIONEER programme SOUL trial Solved Why an oral GLP-1 agonist is a formulation achievement more than a chemistry one I have a specific reason for asking rather than idle curiosity, and the context is below. A methods question rather than a…	+130	135	11k	7mo

Related topics — sharing the tags PIONEER programme, orforglipron, randomised trial

Topic	Participants	Replies	Views	Activity
Journal club: STEP 3 and the intensive behavioural therapy floor Evidence › Journal club randomised trial journal club effect size risk of bias Posting this under the heading it deserves: Journal club: STEP 3 and the intensive behavioural therapy floor Everything below is what sits behind that. Two things I would like separated before anyone answers…	+6	10	13k	28d
Journal club: SURMOUNT-OSA and a hard endpoint in a soft field Evidence › Journal club randomised trial effect size journal club risk of bias Solved Posting this under the heading it deserves: Journal club: SURMOUNT-OSA and a hard endpoint in a soft field Everything below is what sits behind that. Collecting what is known about SURMOUNT-OSA in one place,…	+47	51	617	16mo
Open-label extensions: what survives and what does not Evidence › Trials discontinuation & dropout randomised trial estimand Closed Posting this under the heading it deserves: Open-label extensions: what survives and what does not Everything below is what sits behind that. I have spent a fortnight trying to pin open-label extensions down…		4	22k	3mo
What TRIUMPH is designed to answer, and why we should not pre-empt it Compounds › Retatrutide retatrutide effect size TRIUMPH programme preprint Solved What TRIUMPH is designed to answer, and why we should not pre-empt it I have a specific reason for asking rather than idle curiosity, and the context is below. TRIUMPH keeps being re-asked here and I think…	+4	8	142	6h
Food effects on oral incretin absorption: what is documented Compounds › Oral incretins PIONEER programme SOUL trial randomised trial oral semaglutide Solved Under review On the subject in the title: Food effects on oral incretin absorption: what is documented Working notes rather than a conclusion. Food effects on oral incretin, from the point of view of someone who has read…		2	4.4k	12mo

Sponsored PeptideMeter — peptide analytics and supplier verificationPurity analysis and structured supplier verification, published as dated records rather than scores. Referenced throughout our sourcing documentation.View analytics →