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What is the reported incidence of vomiting on oral semaglutide in PIONEER-1?

Asked 25 Oct 2024Modified 18 months agoViewed 19k times
39

Details up front: vomiting · oral semaglutide · PIONEER-1.

I can parse the result. I am less sure what it licenses me to conclude.

I have deliberately not looked at anyone else’s interpretation yet.

What does this actually establish, and what does it not?

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askedtwo_point_four8.9k1625 Oct 2024
8Voting to keep this open — it is more specific than it first looks. – nine_point_nine 7 months ago
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5 Answers

Accepted answer first, then by votes
69

Accepted answer

Take it from the PIONEER-1 adverse-event table by arm, and check the unit before you use it. An incidence can be the proportion of participants who reported the event at least once, or the count of events divided by exposure time, and the two differ by however many people had it repeatedly. Then subtract the placebo arm, because the untreated rate is not zero. And read the discontinuation column beside it: an event that made people leave the trial is under-counted at every later visit, so a low late-timepoint incidence can mean the event was severe rather than rare.

The relevant risk chain is vomiting to volume depletion to reduced renal perfusion to a rising creatinine, which is how most acute renal events in this class occur.

Oral rehydration solutions work by glucose-coupled sodium co-transport, which continues to function when secretion is deranged. That is why the glucose-to-sodium ratio matters and a high-sugar sports drink is not equivalent.

The part that matters: warning signs that convert this from a nuisance to a clinical problem: inability to keep fluids down for more than a few hours, reduced urine output, dizziness on standing, confusion, or severe abdominal pain.

Vomiting rates in the trial programmes are reported separately from nausea and are consistently lower and more dose-dependent.

Rinse rather than brush after an episode. Enamel is not replaceable.

edited 26 Dec 2024 by Dr_Lena_Ostrowska — tightened the wording; no substantive change

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DO
answered · acceptedDr_Lena_Ostrowska38k2727 Nov 2024
3The red-flag list should be higher up the answer, not at the bottom. – tandem_gradient 5 months ago
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28

The short version: usually escalation-related, usually self-limiting, and dangerous mainly through dehydration.

Trial incidence for vomiting runs at roughly a third to a half of the nausea rate depending on agent and dose, and it is more concentrated in the escalation phase than nausea is.

Fluid lost in vomit carries sodium at roughly 60 millimoles per litre and potassium at rather less, so replacing it with plain water alone dilutes plasma sodium rather than restoring balance.

Anti-emetics interact with other medication and are a prescriber decision.

If fluids will not stay down for several hours, that is the threshold. Get help.

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DL
answeredDr_Otto_Lindqvist72k5816 Nov 2024
7Adding for future readers: fluids between meals rather than with them made a real difference. – RP_C18 3 months ago
6Same experience here, different supplier. – fib4_reader 28 days ago
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22

The honest answer is that a day of it is unpleasant and that several days of it needs help.

Dental enamel erosion from repeated vomiting is a real if unglamorous consequence; rinsing with water rather than brushing immediately is the standard advice.

In practice, a practical home formulation is about six level teaspoons of sugar and half a level teaspoon of salt in one litre of water, taken in small frequent sips rather than in volumes that provoke another episode.

Electrolyte composition of gastric and intestinal secretions is published and is the basis for replacement calculations.

The renal risk here is volume, not toxicity. That is the mechanism to watch.

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TA
answeredtri_gly_ala24k3820 Dec 2024
16

To be exact about it, anti-emetics are a clinical decision and not a self-management step.

An episode of vomiting several days after a dose, with no escalation and no other explanation, is not the typical pattern and deserves attention rather than tolerance.

Oral rehydration solution composition is standardised by the World Health Organization and rests on glucose-coupled sodium transport.

Do not escalate the dose while this is happening.

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DB
answeredDr_Signe_Baldursdottir29k2711 Feb 2025
-3

Answer first: vomiting is less common than nausea, is more strongly dose-related, and matters chiefly because of what it does to fluid and electrolyte balance.

Repeated vomiting is the mechanism behind most reported acute kidney injury in this class. The renal event is a volume event, not a direct toxicity.

Volume depletion as the mechanism for acute creatinine rise is basic renal physiology and explains the pattern of renal reports in this class.

Research-use material is not approved for human use, and an unverified dose is an unquantifiable variable in any of this.

Small frequent sips of an oral rehydration solution, not large volumes of water.

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DO
answeredDr_Lena_Ostrowska38k279 Dec 2024

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.