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What does SURPASS-3 tell me about early satiety at the 15 mg dose?

Asked 31 May 2025Modified 11 months agoViewed 11k times
26

For reference: SURPASS-3 · early satiety · 15 mg.

I have the document in front of me and I can read the numbers. What I cannot do is interpret them.

I am reasonably comfortable with statistics and completely uncomfortable with chromatography, or vice versa.

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

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LS
askedlukas_sedlacek16k1831 May 2025
3Voting to keep this open — it is more specific than it first looks. – Dr_Ilse_Vandenberg 9 months ago
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5 Answers

Accepted answer first, then by votes
87

Accepted answer

Only what the 15 mg arm reported, and the denominator is that arm rather than the trial. Adverse-event tables are published per arm, so the 15 mg incidence of early satiety 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 — early satiety occurs in people who received nothing, and the difference is the part attributable to the drug. And check whether SURPASS-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.

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.

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.

Relative to absolute, worked

QuantityValueDerivation
Control-arm event rate8.0 %From the trial table, not the abstract
Hazard ratio0.80Reported
Treated event rate6.4 %8.0 × 0.80
Absolute risk reduction1.6 pp8.0 − 6.4
Number needed to treat631 ÷ 0.016
Relative risk reduction20 %1 − 0.80

The last two rows describe the same finding. Only one of them is used in headlines.

To be exact about it, 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.

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.

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

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RH
answered · acceptedrania_haddad13k2724 Aug 2025
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35

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.

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.

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.

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.

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

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TQ
answeredtriple_agonist_q57k3813 Aug 2025
24

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.

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.

On the detail: 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.

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

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DC
answereddrawn_and_capped12k172 Aug 2025
2Good answer, but the confidence interval in the cited trial is wider than implied. – k_szabo 7 months ago
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20

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

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.

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.

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TQ
answeredtriple_agonist_q57k3822 Jul 2025
3The number needed to treat is the framing that finally made this concrete for me. – jonas_ekstrom 2 months ago
2Worth flagging that this changed with the 2025 publication, so older answers are out of date. – ines_brandt 24 days ago
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19

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.

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.

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

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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IB
answeredilaria_bertone33k3811 Jul 2025
2Which population was that figure from? It moves a lot between the trials. – ines_brandt 3 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.