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What is the reported incidence of constipation on a GLP-1 receptor agonist in SURPASS-3?

Asked 13 Dec 2024Modified 16 months agoViewed 24k times
10

What I am working with: constipation · a GLP-1 receptor agonist · SURPASS-3.

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?

constipation
constipation

Slowed transit as a consequence of delayed gastric emptying and reduced intake: incidence figures, fibre and hydration evidence, and why it often…

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clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

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EM
askedeoin_mcgarry18k3813 Dec 2024
6Worth saying whether you are keeping fluids down, because that changes the answer. – Dr_Marek_Zielinski 4 months ago
5How severe, and does anything relieve it? Both matter for what people will say. – Dr_Ingrid_Baumgartner 3 months ago
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5 Answers

Accepted answer first, then by votes
48

Accepted answer

Take it from the SURPASS-3 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 honest answer is that this needs an active plan rather than waiting, since it does not usually resolve on its own.

Physical activity has a modest but real effect on transit time and is free, which makes it worth including even though it will not fix this on its own.

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.

Aim for 25 to 30 grams of fibre a day, which requires deliberate planning at a reduced total intake because fibre-rich foods are bulky and satiating exactly when appetite is suppressed.

The fibre-and-fluid relationship in functional constipation is established across intervention studies, and fibre without adequate fluid worsens symptoms.

Nothing here is medical advice.

Osmotic first, stimulant reluctantly, and not as a standing arrangement.

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DB
answered · acceptedDr_Ingrid_Baumgartner73k584 Apr 2025
3Does the tolerance develop at the same rate for the daily agents? – liam_bracken 8 months ago
2This should be linked from the help pages. – tobias_maartens 6 months ago
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17

Answering this needs the actual fibre and fluid intake, and people are almost always taking less of both than they think.

Magnesium-containing preparations act osmotically and are widely used; they are a laxative rather than a supplement in this context, and the dose is what makes the difference.

To be exact about it, red flags that change this from a management question to a clinical one: no bowel movement for several days with abdominal distension and vomiting, blood in the stool, or unexplained weight loss beyond what is expected.

This one does not attenuate with tolerance. Plan for it rather than waiting it out.

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RP
answeredravi_pillai12k1716 Dec 2024
6The red-flag list should be higher up the answer, not at the bottom. – halvard_ness 42 days ago
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12

To be exact about it, severe abdominal pain with no bowel movement and vomiting is a different problem entirely and is urgent.

Soluble fibre — psyllium, oats, legumes — holds water and softens stool. Insoluble fibre adds bulk and speeds transit. In slowed-transit constipation the soluble kind is generally the more useful of the two.

Stimulant laxatives are effective and are not a first choice for a problem that is going to persist for months, because of tolerance and dependence concerns with regular use.

Physical activity has a small measurable effect on colonic transit time in controlled studies.

The caveat is that obstruction is a surgical emergency and presents as pain, distension and vomiting rather than as ordinary constipation.

25 to 30 grams a day, deliberately planned, because it will not happen by accident.

edited 28 Jan 2025 by ines_brandt — corrected a unit error in the worked example

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IB
answeredines_brandt113k2577 Jan 2025
11

The relevant mechanism is that slowed transit plus a smaller, drier stool is a combination that both reduces frequency and increases effort.

Osmotic agents such as macrogol draw water into the lumen and are the usual first pharmacological step; they work with the mechanism rather than against it.

Osmotic laxatives such as macrogol have the strongest evidence base for chronic constipation and are first-line in most guidelines.

Fibre and fluid together. Fibre alone makes it worse and that is the commonest mistake.

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WO
answeredw_okoye43k13719 Feb 2025
5Adding a vote because this deserves more of them. – tobias_maartens 16 days ago
6This is the first explanation of the timing pattern that has actually made sense to me. – fill_volume 2 months ago
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-1

Adding fibre without adding fluid makes it worse, which is the most common self-inflicted error in this tag.

Adding fibre without adding fluid produces a larger, drier, harder stool and makes the problem worse. The fluid is not optional and is the step people skip.

Constipation is reported consistently across the trial programmes in this class, generally at rates below nausea, and does not show the same attenuation over time.

Pain, distension and vomiting together are urgent. That is not constipation.

edited 29 Dec 2024 by esther_vandeVelde — added a caveat about sampling

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EV
answeredesther_vandeVelde52k2727 Dec 2024
8Any published figure for how long the constipation persists, given it does not attenuate? – siobhan_deasy 9 months ago
7Worth flagging that this presents differently in people who titrated faster than the label. – plate_count_9k 7 months ago
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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.