What is the reported incidence of headache on semaglutide in STEP 5?

Stated plainly: headache · semaglutide · STEP 5.

I would like help reading this properly rather than being told what conclusion to reach.

I have the full report including the method section, so I can quote specifics if that helps.

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

Take it from the STEP 5 adverse-event table by arm, and check the unit before you use it. An incidence can be the proportion of participants who reported the event at least once, or the count of events divided by exposure time, and the two differ by however many people had it repeatedly. Then subtract the placebo arm, because the untreated rate is not zero. And read the discontinuation column beside it: an event that made people leave the trial is under-counted at every later visit, so a low late-timepoint incidence can mean the event was severe rather than rare.

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

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.

Headline results, principal programmes

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.

If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.

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.

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.

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

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.

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 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.

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.

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.

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.

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

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.

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.

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