Accepted answer
Check the STEP 2 inclusion criteria against yourself in that order: entry BMI band, diabetes status, prior weight-loss attempts, and what the run-in excluded. Registration programmes recruit a population selected to show an effect if one exists, which is the right design and a poor basis for generalising. The run-in is the part that is easiest to miss: a programme that drops people during a placebo lead-in has already removed those least likely to tolerate or comply, and the published arms describe the survivors. External validity is not a property of the trial; it is a property of the distance between its population and yours, and that distance is yours to measure.
In practice, 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
| Trial | Agent | n | Duration | Primary result |
|---|
| STEP 1 | Semaglutide 2.4 mg | 1,961 | 68 wk | −14.9 % vs −2.4 % weight |
| STEP 2 | Semaglutide 2.4 mg, T2DM | 1,210 | 68 wk | −9.6 % vs −3.4 % weight |
| SURMOUNT-1 | Tirzepatide 5/10/15 mg | 2,539 | 72 wk | −15 / −19 / −21 % weight |
| SURMOUNT-4 | Tirzepatide, withdrawal | 670 | 88 wk | Continued loss vs substantial regain |
| SELECT | Semaglutide 2.4 mg | 17,604 | ~40 mo | MACE HR 0.80 (0.72–0.90) |
| FLOW | Semaglutide 1.0 mg, CKD | 3,533 | ~3.4 yr | Renal composite reduced; stopped early |
| SURMOUNT-OSA | Tirzepatide, OSA | 469 | 52 wk | AHI reduced with and without PAP |
The underlying point is that 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.
Be careful about generalising from a trial population to yourself. The exclusion criteria are usually the most informative page in the supplement.
The short version: check the endpoint, check the comparator, check who was excluded, then look at the number.