This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.
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.
Reading it back, the second half matters more than the first.
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.
If that is already documented somewhere, ignore me and link it.
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.
On post #90 — agreed on the reasoning, with one qualification.
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.
Timing consistency matters more for oral dosing than for weekly injection, because absorption depends on the state of the stomach and the state of the stomach varies through the day.
This is the version I would want a new member to read first.
This follows post #96 rather than contradicting it.
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.
Worth separating two things that post #94 runs together.
Before the thread moves on from SOUL trial and oral semaglutide — what is the sample size behind the claim? I am not being difficult; I have seen the same figure quoted from an n of four and from an n of four hundred.
PIONEER programme is phase 3 for oral semaglutide. The trials cover multiple indications and durations. Reading them requires attention to which trial is which because they are not all the same question.
I read post #98 twice before replying, because I had assumed the opposite.
The gastrointestinal tolerability profile of the oral formulation is broadly similar in character to the injectable, which supports the effects being systemic rather than local irritation.
A weak preference rather than a position.
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.
I would want a second opinion before relying on that.
The claim about SOUL trial and oral semaglutide upthread is stronger than its source supports. I have read the source. The source says "associated with" and the post says "causes".
Building on post #102 rather than restating it.
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.
That is all the detail I have. Someone else will have more.
SOUL trial and oral semaglutide: I would want to see the raw numbers rather than the summary before agreeing. Summaries lose exactly the information that would settle this.
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
Orforglipron as a non-peptide: what changes when the molecule is small
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 |
|
SNAC and the mechanism of oral peptide absorption
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
On the subject in the title: Dose numbers for oral formulations are not comparable to injectable ones Working notes rather than a conclusion. Putting the numbers in the first post, because a question about a…
|
+19 | 23 | 39k | 6mo |
|
About the Oral incretins category
Oral semaglutide, orforglipron and the absorption problem. PIONEER and OASIS data. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is recorded with its author…
|
4 | 6.2k | 20d | |
|
Oral versus injectable exposure: comparing apples to a different fruit — a second dataset
Posting this under the heading it deserves: Oral versus injectable exposure: comparing apples to a different fruit — a second dataset Everything below is what sits behind that. Something about Oral versus…
|
+27 | 31 | 17k | 25d |
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
About the Oral incretins category
Oral semaglutide, orforglipron and the absorption problem. PIONEER and OASIS data. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is recorded with its author…
|
4 | 6.2k | 20d | |
|
Coming back to: Why semaglutide solutions can look faintly opalescent and when that matters
Asking directly, because I could not find a straight answer: Why semaglutide solutions can look faintly opalescent and when that matters Reading back through what has been written here about semaglutide…
|
+16 | 20 | 17k | 13mo |
|
Second pass at: Cagrilintide's dosing interval and the pharmacokinetics behind it
On the subject in the title: Second pass at: Cagrilintide's dosing interval and the pharmacokinetics behind it Working notes rather than a conclusion. A comparison question rather than a question about one…
|
+2 | 6 | 2.4k | 7mo |
|
What SELECT changed about how semaglutide is discussed, and what it did not
Asking directly, because I could not find a straight answer: What SELECT changed about how semaglutide is discussed, and what it did not I was wrong about SELECT in a thread last spring and I would like to…
|
+120 | 132 | 2k | 14mo |
|
Second pass at: Reading a trial's population section before its results
Second pass at: Reading a trial's population section before its results Writing it up because I had to work it out twice and would rather nobody else did. Reading STEP 1 ( N Engl J Med , 2021) for the…
|
4 | 9.5k | 10h |