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

Asked 21 Sept 2025Modified 7 months agoViewed 7.7k times
19

Conditions: SURPASS-3 · dizziness · 15 mg.

The figures are clear enough; the question is what they mean and what they do not.

I can supply the numbers if the specifics change the answer.

What would I need in addition before this supported a decision?

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askedcake_intact17k2721 Sept 2025

5 Answers

Accepted answer first, then by votes
48

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 dizziness 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 — dizziness 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.

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.

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 underlying point is that 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.

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

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answered · acceptedDr_Nadia_Farsi104k24726 Dec 2025
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17

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.

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 part that matters: 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.

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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answeredh_villanueva70k486 Jan 2026
6Thank you — this is the answer I was looking for. – Dr_Lena_Ostrowska 2 months ago
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13

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

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.

The underlying point is that 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.

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

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

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answerednoor_alhassan11k274 Dec 2025
6The number needed to treat is the framing that finally made this concrete for me. – halvard_ness 29 days ago
7The exclusion criteria are the most informative page in the supplement and nobody reads them. – tandem_gradient 3 months ago
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11

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.

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.

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 1 Dec 2025 by Dr_Nadia_Farsi — added the method parameters

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answeredDr_Nadia_Farsi104k24712 Nov 2025
3Worth flagging that this changed with the 2025 publication, so older answers are out of date. – Dr_Fatima_Belkacem 3 months ago
2Is the open-label extension included in that figure, or just the randomised phase? – tamsin_wray 29 days ago
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10

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

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.

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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answeredDr_Rosalind_Achebe69k14715 Dec 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.