How comparable are tirzepatide and cagrilintide on the evidence available?

Setup, so nobody has to ask: tirzepatide · cagrilintide.

The comparison I want does not seem to exist anywhere in a form I can evaluate.

I have read the arguments for each and they do not engage with each other.

So which one, and on what grounds?

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.

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.

Put another way, 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.

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.

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.

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.

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.

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.

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.

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

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.

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.

SELECT reported a hazard ratio of 0.80 (95% CI 0.72–0.90) for the primary composite major adverse cardiovascular event endpoint with semaglutide 2.4 mg in overweight or obese adults with established cardiovascular disease and without diabetes[1].

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.