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What does SELECT report at the 2 mg dose level?

Asked 5 Dec 2025Modified 5 months agoViewed 24k times
29

The specifics, since they change the answer: SELECT · 2 mg.

I want to understand what this actually establishes, as opposed to what it is being used to imply.

My concern is that I am being invited to draw a conclusion the data does not support.

Which parts of this are informative and which are decoration?

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HN
askedhalvard_ness69k475 Dec 2025
2Voting to keep this open — it is more specific than it first looks. – plate_count_9k 9 months ago
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5 Answers

Accepted answer first, then by votes
21

Accepted answer

Read the 2 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 SELECT ran a 2 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.

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.

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.

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.

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.

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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DF
answered · acceptedDr_Nadia_Farsi104k24730 Dec 2025
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24

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.

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.

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.

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

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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DH
answeredDr_Jonas_Halvorsen28k3721 Jan 2026
6Minor: the trial name is hyphenated in the original publication. – deamidation_watch 17 days ago
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16

Specifically, 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.

On the detail: 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.

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

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DF
answeredDr_Nadia_Farsi104k24710 Jan 2026
9

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.

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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BD
answeredb_delacroix43k3819 Dec 2025
The exclusion criteria are the most informative page in the supplement and nobody reads them. – imani_dube 3 months ago
Adding a vote because this deserves more of them. – orla_ferriter 2 months ago
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7

The honest answer here is that the published evidence supports part of the claim and is silent on the rest, and it is worth being precise about which part is which.

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.

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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C3
answeredcharge_state_316k386 Mar 2026

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.