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What is the reported incidence of early satiety on oral semaglutide in SOUL?

Asked 12 Jun 2024Modified 22 months agoViewed 51k times
23

Conditions: early satiety · oral semaglutide · SOUL.

I have read the primary source rather than the summary, which has left me with more questions.

I understand the headline. I do not understand the footnotes, and the footnotes look important.

How should I read this, and where are the traps?

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DC
askedDr_Idris_Coulibaly33k13712 Jun 2024
Worth saying whether you are keeping fluids down, because that changes the answer. – ruaidhri_o_shea 9 months ago
8How severe, and does anything relieve it? Both matter for what people will say. – kwn_analytical 7 months ago
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5 Answers

Accepted answer first, then by votes
79

Accepted answer

The honest answer is that the first eight weeks are the hard part and that most people who get through them stop having the conversation.

Symptom prevalence in trials, broadly: nausea a quarter to a half, diarrhoea and constipation each roughly ten to twenty per cent, vomiting rather less, with all rates rising with dose.

Gastrointestinal adverse events, indicative pooled rates

EventActive armPlacebo armTiming
Nausea40–45 %15–20 %Peaks 1–2 wk after each step
Vomiting15–25 %5–8 %Follows nausea
Diarrhoea20–30 %10–15 %Early, variable
Constipation20–25 %8–12 %Later onset, persistent
Discontinuation for GI events4–7 %1–2 %Mostly during escalation

Ranges span agents and doses; read the specific prescribing information for a specific figure.

Anticipating a slower-than-label titration from the start is a legitimate approach and costs only time, since the exposure ceiling is the same.

Trial-reported incidence and discontinuation rates for gastrointestinal effects are published per agent and per dose and are the appropriate figures to quote.

Smaller meals, less fat, fluids between rather than with. In that order.

edited 14 Jul 2024 by fiadh_cronin — removed a claim I could not source

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answered · acceptedfiadh_cronin58k5813 Jul 2024
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70

The relevant physiology is that gastric emptying slows substantially and then partially normalises with continued exposure at a stable dose.

Gastric emptying of a solid meal can be delayed substantially at initiation. The effect is largest early and attenuates over weeks for the long-acting agents, which is the mechanistic basis for the titration schedule.

The practical hierarchy of interventions: slow the titration, reduce meal size, reduce fat, separate fluids from meals, and only then consider symptomatic treatment.

Nothing here is medical advice.

Everything except constipation attenuates. Plan differently for that one.

edited 14 Jul 2024 by Dr_Colm_Fitzhenry — expanded the table to cover the lower concentration

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DF
answeredDr_Colm_Fitzhenry69k2471 Jul 2024
37

Answering this needs the titration history, because going faster than the schedule is the single largest modifiable factor.

Discontinuation for gastrointestinal effects in the trials runs in the low single-figure percentages, which means the great majority of people who experience these effects continue.

Symptoms that appear for the first time at a stable dose after months are not the ordinary pattern and warrant looking for another explanation.

Four-weekly titration intervals in the licensed schedules were selected to allow tolerance between escalations.

The caveat is that severe persistent symptoms, particularly with dehydration or severe pain, are clinical and not a matter of waiting them out.

Most people who report these effects continue. The discontinuation rate is low.

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DL
answeredDr_Otto_Lindqvist72k5824 Jul 2024
6Thank you — this is the answer I was looking for. – v_ramaswamy 8 months ago
5Small correction: the discontinuation rate in the trials is lower than most people assume. – marta_okonkwo 6 months ago
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29

This is the group of effects that drives almost all discontinuation in the trial programmes.

Fat is the macronutrient that slows emptying most on its own, so a high-fat meal on top of pharmacologically delayed emptying is the combination that produces the worst episodes.

Dietary fat slowing gastric emptying is basic gastrointestinal physiology and independent of any drug effect.

New symptoms at a stable dose after months need a different explanation.

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RC
answeredRP_C18105k3484 Aug 2024
2Worth adding that the area postrema explanation also predicts why it settles. – deamidation_watch 3 months ago
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-3

The short version: dose-related, escalation-concentrated, mostly attenuating except for constipation, and manageable by titration pace more than anything else.

Reflux occurs because a slower-emptying stomach retains volume for longer against a lower oesophageal sphincter that has not changed. Smaller meals and not lying down within a few hours are the direct responses.

Gastric emptying studies in this class quantify the delay directly and document its attenuation with continued exposure to the long-acting agents.

Slow the titration first. It is the intervention with the best evidence and the lowest cost.

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SD
answeredsunniva_dahl22k2715 Sept 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.