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What is the reported incidence of constipation on tirzepatide in SURMOUNT-4?

Asked 20 Jun 2024Modified 21 months agoViewed 11k times
2

What I am working with: constipation · tirzepatide · SURMOUNT-4.

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.

What can I legitimately conclude from this figure?

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askedfresh_bac9.7k1620 Jun 2024
8Which agent and which dose? The rates differ enough to matter. – anja_hellstrom 8 months ago
7Voting to keep this open — it is more specific than it first looks. – gradient_slope 7 months ago
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5 Answers

Accepted answer first, then by votes
26

Accepted answer

Take it from the SURMOUNT-4 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.

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.

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.

Concretely, 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.

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

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

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answered · acceptedgrainne_ahearn50k388 Sept 2024
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9

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

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.

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.

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

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

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answeredivo_paunovic16k271 Oct 2024
5Does the tolerance develop at the same rate for the daily agents? – Dr_Rosalind_Achebe 7 months ago
6Adding for future readers: fluids between meals rather than with them made a real difference. – Dr_Ingrid_Baumgartner 8 months ago
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8

More usefully, this is the adverse effect that persists longest, because unlike nausea it does not attenuate with tolerance.

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.

Mechanically, 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.

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.

edited 18 Aug 2024 by Dr_Bram_Verhoeven — expanded the table to cover the lower concentration

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answeredDr_Bram_Verhoeven84k24826 Jul 2024
5This is the first explanation of the timing pattern that has actually made sense to me. – h_villanueva 5 months ago
4I have seen this misattributed to the compound twice when it was the deficit. – mz_4113 4 months ago
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8

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

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.

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.

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

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

edited 16 Oct 2024 by sunniva_dahl — clarified the distinction between purity and content

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answeredsunniva_dahl22k2720 Sept 2024
7

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.

The pooled gastrointestinal adverse-event rates across the STEP programme and the SURMOUNT programme are reported in the primary publications and in the FDA and EMA assessment reports, and the assessment reports are more useful because they give the placebo-arm rates alongside the active-arm rates in the same table.

Research-use compounds are not approved for human use.

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

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answeredDr_Colm_Fitzhenry69k24712 Oct 2024
5This should be linked from the help pages. – charge_state_3 2 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.