How comparable are cagrilintide and liraglutide on the evidence available?

Stated plainly: cagrilintide · liraglutide.

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.

So which one, and on what grounds?

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

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.

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.

This is answerable from the published record, but only if you take the placebo arm seriously rather than reading the active arm alone.

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.

On the detail: 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.

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.

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.

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.

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.

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.

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.

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

edited 6 Jan 2025 by pierce_count — removed a claim I could not source