Conditions: liraglutide · tirzepatide.
I am trying to choose between two options that are usually discussed as though only one exists.
I am not optimising for price, but I am not indifferent to it either.
So which one, and on what grounds?
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.
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.
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 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.
If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsStart 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.
Concretely, 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.
Meta-analyses in this area are dominated by whichever trial contributed the most participants, so read the forest plot rather than the summary estimate.
When two sources disagree, the answer is almost always in the methods section of the one you have not read.
It helps to be literal here: this is answerable from the published record, but only if you take the placebo arm seriously rather than reading the active arm alone.
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.
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.
I am not a clinician and this is not medical advice; it is a reading of a published protocol.
Read the protocol and the statistical analysis plan if the result matters to you. Both are usually published alongside.
edited 30 May 2025 by Dr_Ilse_Vandenberg — added a caveat about sampling
Look at the discontinuation rate alongside the efficacy figure. A large effect in the two thirds who stayed is a different result from a large effect in everyone.
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.
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.
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.
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.
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.
edited 30 Aug 2025 by coring_risk — added the placebo-arm figures
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.