Trial data comparison (revision 31)
Old revision·21:07, 12 May 2025·StabilityStig
| Trial data comparisonInteractive reference tool | |
|---|---|
Effect sizes from separate trials. Placing them side by side is not a head-to-head comparison. | |
| Rows | Major randomised trials of incretin agonists |
| Columns | Population, n, duration, comparator, endpoint, result |
| Caveats | |
| Head-to-head? | Only where the comparator column says so |
| Estimand | Stated per row where known |
| Populations | Differ substantially between trials |
| Reference tool infobox · conventions | |
The trial data comparison tabulates the principal published results of the major randomised trials of GLP-1 receptor agonists and related compounds, so that a reader arriving at one figure can see the others alongside it. Each row is attributed to its trial, arm, duration and comparator.
The table is easy to misread in one specific way, and the article exists partly to prevent it. Two figures from two trials are not a comparison of two drugs. Trial populations differ in baseline weight, glycaemic status, diabetes duration, background therapy and geography; durations differ; and the statistical estimand used to summarise a weight-change endpoint differs between publications and sometimes within a single one.[1] A larger number in this table means a larger result in that trial, and nothing more.
Where a genuine head-to-head randomised comparison exists — SURPASS-2 compared tirzepatide with semaglutide 1 mg directly — the comparator column says so, and only those rows support a statement that one agent outperformed another.[2]
The comparison
[edit]Filter by compound, trial programme or endpoint type. The bar is drawn to the magnitude of the primary result and is scaled within its endpoint type only.
Why the estimand matters
[edit]A weight-change endpoint can be summarised in at least two defensible ways, and the ICH E9(R1) addendum names them.[1]
The treatment-policy estimand asks what happened to everyone randomised, including those who stopped the drug and those who started another one. It answers "what does prescribing this achieve", and it is the more conservative figure.
The trial-product estimand asks what happened while participants were taking the drug as intended. It answers "what does the molecule do", and it is the larger figure.
The gap between them is not small. In the STEP programme the two estimands for the same trial differed by roughly one to two percentage points of body weight, which is a difference of the same order as the gap between some of the drugs being compared.[3] A table that mixes estimands between rows therefore manufactures apparent differences between compounds that are artefacts of the analysis choice.
| Estimand | Question answered | Effect on the figure |
|---|---|---|
| Treatment policy | What prescribing achieves | Smaller; includes discontinuations |
| Trial product | What the molecule does on treatment | Larger; censors discontinuation |
| Not stated | — | Unusable for comparison |
See also
- STEP trial programme
- SURMOUNT trial programme
- SURPASS trial programme
- SELECT trial
- Intention-to-treat analysis
References
- ^ a b International Council for Harmonisation, E9(R1): Addendum on Estimands and Sensitivity Analysis in Clinical Trials (2019).
- ^ Frías JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes." New England Journal of Medicine 385(6):503–515 (2021). DOI:10.1056/NEJMoa2107519. PMID 34170647.
- ^ Wilding JPH, Batterham RL, Calanna S, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine 384(11):989–1002 (2021). DOI:10.1056/NEJMoa2032183. PMID 33567185.