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What does SURPASS-3 tell me about hair thinning at the 5 mg dose?

Asked 16 Apr 2026Modified 2 months agoViewed 6.6k times
9

For reference: SURPASS-3 · hair thinning · 5 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 is the correct interpretation, and what is the common misreading?

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CL
askedcap_the_luer14k2716 Apr 2026

5 Answers

Accepted answer first, then by votes
74

Accepted answer

Only what the 5 mg arm reported, and the denominator is that arm rather than the trial. Adverse-event tables are published per arm, so the 5 mg incidence of hair thinning 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 — hair thinning 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.

It helps to be literal here: 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.

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.

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.

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

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answered · acceptedforty_units16k174 May 2026
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21

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.

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.

It helps to be literal here: 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.

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

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DB
answeredDr_Ingrid_Baumgartner73k5812 May 2026
2Good answer, but the confidence interval in the cited trial is wider than implied. – rania_haddad 3 months ago
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17

Worth being precise here: 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.

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.

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.

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

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TU
answeredtenth_of_a_unit57k3716 May 2026
6This matches what I was told by a clinician, for whatever that is worth. – v_ramaswamy 25 days ago
7Minor: the trial name is hyphenated in the original publication. – orla_ferriter 2 months ago
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16

Look at the discontinuation rate alongside the efficacy figure. A large effect in the two thirds who stayed is a different result from a large effect in everyone.

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.

edited 28 May 2026 by Dr_Jonas_Halvorsen — added the placebo-arm figures

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DH
answeredDr_Jonas_Halvorsen28k3720 May 2026
-2

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.

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.

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.

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 May 2026 by Dr_Ingrid_Baumgartner — added a caveat about sampling

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DB
answeredDr_Ingrid_Baumgartner73k588 May 2026
2The exclusion criteria are the most informative page in the supplement and nobody reads them. – coring_risk 8 months ago
3Adding a vote because this deserves more of them. – Dr_Jonas_Halvorsen 9 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.