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What does SURMOUNT-3 report at the 15 mg dose level?

Asked 12 Apr 2025Modified 12 months agoViewed 11k times
This question was marked as a duplicate of What does FLOW report at the 2.4 mg dose level?Closed 24 Apr 2025. It remains here because the answers below are specific to how it was asked.
5

Stated plainly: SURMOUNT-3 · 15 mg.

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 would I need in addition before this supported a decision?

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LM
askedlucia_marchetti19k2712 Apr 2025
3Same situation here, so I will follow this one. – Dr_Malik_Osei 3 months ago
2Which trial, and which endpoint? The question is answerable once those are named. – h_pergande 2 months ago
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5 Answers

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74

Read the 15 mg row, not the pooled one. A programme that randomised more than one dose level reports each arm separately, and the figure that circulates afterwards is usually either the top-dose arm or an average across arms nobody was randomised to. If SURMOUNT-3 ran a 15 mg arm, that row carries its own sample size and its own confidence interval, and both are narrower than the trial-level ones by roughly the square root of however many arms there were. Take the primary publication rather than the press release: one reports by arm, the other reports whichever number is largest. A dose level inside a trial is a protocol decision made under supervision, not a recommendation, and nothing here is medical advice.

The trial answers a narrower question than the headline suggests, and the narrowing is where the useful information is.

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.

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.

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.

I am not a clinician and this is not medical advice; it is a reading of a published protocol.

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

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answeredDr_Idris_Coulibaly33k13720 May 2025
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48

Start with what the trial was powered for. Everything else in the publication is secondary, exploratory, or a subgroup, and those three words mean three different things.

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.

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.

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.

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

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DR
answeredDr_Priya_Raghunathan49k13731 May 2025
39

Stated carefully, a trial establishes what happened to a defined group under a defined protocol. Extending it beyond that group is inference, and inference is allowed as long as it is labelled.

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.

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.

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.

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

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DV
answeredDr_Ilse_Vandenberg113k24826 May 2025
6The placebo-arm figure is the part everyone omits. – laminar_bench 3 months ago
5Which population was that figure from? It moves a lot between the trials. – g_paskevicius 32 days ago
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31

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

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.

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

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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OF
answeredorla_ferriter89k1486 Jun 2025
4Absolute risk reduction rather than relative would make this much more useful. – harriet_lonsdale 5 months ago
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27

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.

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.

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

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answeredplate_count_9k78k2484 Aug 2025

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.