Accepted answer
Whatever its primary endpoint was, at the power it was designed for, in the population it recruited — and nothing else. TRIUMPH-1 was sized to answer one question. Every other result in it is a secondary or exploratory endpoint, powered incidentally if at all, and a nominally significant secondary in a programme with twenty of them is what you would expect from chance alone. So the reading order is: primary endpoint, then whether the secondaries were pre-specified and hierarchically tested, then everything else as hypothesis-generating. A trial establishes one thing well and suggests several things badly, and the press coverage inverts that ranking reliably.
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.
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.
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.
When two sources disagree, the answer is almost always in the methods section of the one you have not read.
edited 18 Jul 2026 by Dr_Ilse_Vandenberg — removed a claim I could not source
5The number needed to treat is the framing that finally made this concrete for me. – micron22 10 months ago add a comment