Numbers first: a GLP-1 receptor agonist · tirzepatide.
I have used one of these for a while and I am considering switching, which requires a reason.
What I care about is reproducibility, because a result I cannot repeat is not useful to me.
What does each option buy me, and what does it cost me?
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.
| Quantity | Value | Derivation |
|---|---|---|
| Control-arm event rate | 8.0 % | From the trial table, not the abstract |
| Hazard ratio | 0.80 | Reported |
| Treated event rate | 6.4 % | 8.0 × 0.80 |
| Absolute risk reduction | 1.6 pp | 8.0 − 6.4 |
| Number needed to treat | 63 | 1 ÷ 0.016 |
| Relative risk reduction | 20 % | 1 − 0.80 |
The last two rows describe the same finding. Only one of them is used in headlines.
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.
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.
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.
Read the protocol and the statistical analysis plan if the result matters to you. Both are usually published alongside.
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsThe trial answers a narrower question than the headline suggests, and the narrowing is where the useful information is.
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 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.
The short version: check the endpoint, check the comparator, check who was excluded, then look at the number.
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.
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.
More usefully, 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.
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.
If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.
edited 10 Sept 2024 by lyoph_cake — corrected a unit error in the worked example
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.
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.
Quote the interval alongside the estimate and half the disagreements on this site would not start.
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.
Be careful about generalising from a trial population to yourself. The exclusion criteria are usually the most informative page in the supplement.
When two sources disagree, the answer is almost always in the methods section of the one you have not read.
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.