Topic summary

Dose numbers for oral formulations are not comparable to injectable ones — a second dataset

Compounds › Oral incretins randomised trial orforglipron PIONEER programme

This is a generated summary. It shows the 8 most-liked posts from a topic of 53, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.

st.dialloTL230 Dec 2024 · edited#7

e.ndiaye, post #3: Anyone comparing published oral and injectable efficacy should check whether the comparison is within one trial or across two. Across two, the populations differ and the comparison is weak. The short version is the first sentence; the rest is why. Go to post

Worth separating two things that post #5 runs together.

Missed doses behave differently for a daily oral than for a weekly injection. With a short interval you are near a trough rather than perturbing a slowly moving average, and the labelling reflects that.

27 likes in reply to #3 19mo

n.boatengTL23 Jan 2025#18

Worth separating two things that post #16 runs together.

Research-use-only oral material is not a licensed tablet and there is no reason to assume it carries a functioning absorption-enhancement system at all. The formulation is most of the product here.

26 likes 19mo

mira.patelTL4 Admin5 Jan 2025#23

crossover_review, post #19: On variability: the between-person spread in exposure for oral semaglutide is wide enough that two people on the same dose can have quite different plasma concentrations. That is inherent to the absorption route. Not the whole picture, but the part of it I can speak to. Go to post

Taking the oral product with more water than instructed reduces absorption rather than helping it. That is counter-intuitive and it is one of the few dosing instructions in this field with a clear pharmacokinetic basis.

I would put this at better than even and not much better.

25 likes in reply to #19 19mo

OstrowskiTL2Member8 Jan 2025#30

Post #28 is the version of this I will quote in future. One addition.

The absorption enhancer in the licensed oral product works by transiently raising local gastric pH and promoting absorption across the mucosa. It is the reason the fasting and water-volume instructions are specific rather than cautious.

26 likes 19mo

BBramleyTL3Regular10 Jan 2025#36

Ostrowski, post #30: Post #28 is the version of this I will quote in future. One addition. The absorption enhancer in the licensed oral product works by transiently raising local gastric pH and promoting absorption across the mucosa. It is the reason the fasting and water-volume instructions are specific rather than cautious. Go to post

I had written a reply contradicting post #34 and deleted it. Here is what survived.

Why administration conditions matter for oral semaglutide and not for injectables: the oral formulation depends on a transient pH effect in the stomach. Anything that changes gastric pH or transit time changes absorption. Food does both.

28 likes in reply to #30 19mo

PSkarbekTL3Regular11 Jan 2025#40

b.fonseca, post #22: Trial adherence in an oral trial with strict administration requirements is genuinely worse than trial-published data often suggests. That is why the exposure variability in oral formulations is mentioned repeatedly in the discussions here. Adding this to the thread rather than to the wiki, because I am not confident enough for the wiki. Go to post

Noted, and I have changed what I was going to do on the strength of it.

21 likes in reply to #22 19mo

cohort_driftTL3Regular12 Jan 2025#42

t.tulloch, post #33: This follows post #32 rather than contradicting it. SNAC is the sodium N-(8-[2-hydroxybenzoyl]amino) caprylate, an absorption enhancer that transiently raises local pH in the stomach and promotes gastric mucosal absorption. Without it, oral bioavailability of semaglutide would be too low for clinically useful dosing. Go to post

The arithmetic in post #39 is right; the assumption feeding it is the part to check.

PIONEER 6 is the cardiovascular outcome trial for oral semaglutide and it enrolled a diabetes population at high cardiovascular risk. Quoting it outside that population is an extrapolation.

That is the practical version. The rigorous version is longer and says the same thing.

22 likes in reply to #33 18mo

s.oyelaranTL213 Jan 2025#45

Following, with nothing to contribute beyond having asked the same thing elsewhere.

31 likes 18mo

Read the full topic (53 posts)

This topic was referenced in

Oral semaglutide bioavailability and its variability between peopleCompounds › Oral incretins · 48 replies

Moved from Cagrilintide & amylin analogues by j.mwangi. Category placement is not obvious from outside and getting it wrong is expected. This topic will get better answers here. The move is recorded in the public log citing R7.

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