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What is the reported incidence of dizziness on semaglutide in SELECT?

Asked 20 Oct 2025Modified 6 months agoViewed 23k times
29

What I am working with: dizziness · semaglutide · SELECT.

I can parse the result. I am less sure what it licenses me to conclude.

I have deliberately not looked at anyone else’s interpretation yet.

What is the correct interpretation, and what is the common misreading?

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AB
askedassay_blank45k3820 Oct 2025

5 Answers

Accepted answer first, then by votes
24

Accepted answer

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.

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.

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

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

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DV
answered · acceptedDr_Bram_Verhoeven84k24828 Jan 2026
5Thank you for separating the surrogate from the outcome. That distinction gets lost constantly. – tobias_maartens 9 months ago
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10

The relevant detail is that 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.

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.

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.

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.

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

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DA
answeredDr_Yusuf_Adeyemi54k14717 Jan 2026
8

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.

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

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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HV
answeredh_villanueva70k4822 Oct 2025
7Thank you — this is the answer I was looking for. – carys_meredith 4 days ago
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7

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.

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.

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

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DV
answeredDr_Bram_Verhoeven84k2488 Feb 2026
The placebo-arm figure is the part everyone omits. – lipid_panel_q 9 months ago
2The number needed to treat is the framing that finally made this concrete for me. – h_pergande 21 days ago
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6

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.

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.

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

edited 22 Dec 2025 by lyoph_cake — removed a claim I could not source

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LC
answeredlyoph_cake78k26715 Dec 2025
Worth flagging that this changed with the 2025 publication, so older answers are out of date. – bea_castellanos 7 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.