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What does TRIUMPH-3 tell me about constipation at the 4 mg dose?

Asked 5 Aug 2025Modified 8 months agoViewed 24k times
33

Details up front: TRIUMPH-3 · constipation · 4 mg.

This is presented as though it settles something, and I am not convinced it does.

I have two documents that appear to disagree, which is what prompted this.

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

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FU
askedforty_units16k175 Aug 2025
3Same question, and the two papers I found disagree, which is why I am watching. – cake_collapsed 8 months ago
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5 Answers

Accepted answer first, then by votes
77

Accepted answer

Only what the 4 mg arm reported, and the denominator is that arm rather than the trial. Adverse-event tables are published per arm, so the 4 mg incidence of constipation has its own numerator and its own denominator, and pooling it with the other arms produces a figure that describes nobody. Two further deductions before you use it. Subtract the placebo arm — constipation occurs in people who received nothing, and the difference is the part attributable to the drug. And check whether TRIUMPH-3 counted events or counted participants: one participant with six episodes is one row in a participant count and six in an event count, and the two get quoted interchangeably. Nothing here is medical advice.

Put another way, this is answerable from the published record, but only if you take the placebo arm seriously rather than reading the active arm alone.

Duration decides what can be seen. A 68-week trial can measure weight and glycaemia; it cannot measure anything whose event rate is one per cent per year without enrolling tens of thousands.

A composite endpoint is only as informative as its least serious component. Where a cardiovascular composite combines death, infarction and stroke, ask which component moved, because they are not interchangeable outcomes.

The cardiovascular outcome programme in this class runs to several large randomised trials — LEADER for liraglutide, SUSTAIN-6 and SELECT for semaglutide, REWIND for dulaglutide — and they are the reason the class is discussed as more than a weight intervention.

The caveat is that trial evidence is about licensed product administered under supervision. None of it transfers automatically to research-grade material of unverified content.

Read the protocol and the statistical analysis plan if the result matters to you. Both are usually published alongside.

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answered · acceptedDr_Bram_Verhoeven84k24811 Oct 2025
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31

The short version: the effect is real, the magnitude depends on the population, and the population is usually the part that gets dropped when a result is quoted second-hand.

Confidence intervals matter more than point estimates when two trials disagree. Two studies reporting fifteen and twenty per cent whose intervals overlap heavily have not disagreed about anything.

Mechanically, open-label extensions are not the same evidence as the randomised phase. Once everyone knows what they are taking, the reported outcomes acquire a bias that no analysis fully removes.

Where a result is quoted from a conference abstract rather than a peer-reviewed publication, the numbers routinely move between the two. It is worth checking which one you are reading.

Be careful about generalising from a trial population to yourself. The exclusion criteria are usually the most informative page in the supplement.

The short version: check the endpoint, check the comparator, check who was excluded, then look at the number.

edited 12 Oct 2025 by hana_petrikova — updated for the 2026 guidance change

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HP
answeredhana_petrikova10k1430 Sept 2025
24

The honest answer here is that the published evidence supports part of the claim and is silent on the rest, and it is worth being precise about which part is which.

Trial populations are selected. Exclusion criteria in this class routinely remove people with significant renal impairment, prior pancreatitis and unstable psychiatric illness, which is exactly the population the results are then quoted for.

On the detail: non-inferiority and superiority designs are not interchangeable. A non-inferiority result says the new agent is not meaningfully worse against a pre-specified margin — it does not say it is as good, and it certainly does not say it is better.

One qualification: absence of a signal in a trial of this size is not evidence of absence for a rare event. It is evidence that the event is rarer than the trial could detect.

When two sources disagree, the answer is almost always in the methods section of the one you have not read.

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DC
answereddrawn_and_capped12k173 Nov 2025
2This should be linked from the help pages. – Dr_Nadia_Farsi 28 days ago
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20

Before comparing two trials, check whether they share an endpoint definition. Frequently they do not, and the numbers then are not comparable in any sense.

Intention-to-treat and per-protocol analyses answer different questions. ITT asks what happens if you offer the treatment; per-protocol asks what happens if it is taken as directed. The gap between the two is a measure of how tolerable the protocol was.

Registry entries at ClinicalTrials.gov carry the pre-specified primary endpoint with a timestamp, which is the cheapest available check on whether an endpoint was changed after the data were seen.

Quote the interval alongside the estimate and half the disagreements on this site would not start.

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LM
answeredlucia_marchetti19k2723 Oct 2025
14

Answer first: read the primary endpoint, the comparator and the population before you read the effect size. Almost every argument on this site about a trial is really an argument about one of those three.

Placebo arms in this class are not nothing. Lifestyle-intervention placebo arms in the major obesity trials commonly lose two to three per cent of body weight, so an active-arm figure quoted without its comparator overstates the drug effect by roughly that much.

Meta-analyses in this area are dominated by whichever trial contributed the most participants, so read the forest plot rather than the summary estimate.

If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.

edited 12 Dec 2025 by ivo_paunovic — clarified the distinction between purity and content

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IP
answeredivo_paunovic16k2725 Nov 2025
6Absolute risk reduction rather than relative would make this much more useful. – esther_vandeVelde 6 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.