STEP 8 — trial digest
STEP 8 (JAMA 2022): How does weekly semaglutide compare directly with daily liraglutide?
Citation and design
| Field | Value |
|---|---|
| Trial | STEP 8 |
| Intervention | Semaglutide 2.4 mg weekly versus liraglutide 3.0 mg daily |
| Publication | JAMA, 2022 (first author Rubino) |
| Design | Randomised, open-label for the comparator schedule, 68 weeks |
| Population | Adults with overweight or obesity without diabetes |
This digest summarises the trial and the criticisms our journal club considered material. It is not a substitute for the paper, and where the two differ the paper is right.
The question it set out to answer
How does weekly semaglutide compare directly with daily liraglutide?
Stating the question before the result is a house convention. A great many arguments about this trial are actually arguments about what it was for.
What it found
The cleanest available head-to-head between a weekly and a daily agent in obesity, with both at their licensed obesity doses.
Semaglutide produced greater mean weight reduction. Discontinuation patterns differed between arms.
A useful trial for the argument that the class is not homogeneous.
Criticisms the journal club considered material
- Different dosing schedules cannot be fully blinded, and expectation effects in a weight-loss trial are not negligible.
- Adherence to a daily injectable is systematically worse than to a weekly one, which is part of the comparison rather than a confounder to be removed — but it does mean the trial compares strategies as much as molecules.
These are criticisms of the design and of how the result is used, not of the investigators. Sessions that lose that distinction get moderated.
How it is misused
The two recurring misuses of this trial in general discussion are quoting the relative effect without the absolute one, and extending the result to a population the trial did not enrol. Both are easy to correct and both keep happening.
Where a number appears in secondary coverage without an estimand attached, assume it is whichever version is larger and check the paper.
Maintenance
Digests are reviewed when new analyses of the same trial are published, and at the review date shown above regardless. If a secondary publication changes the picture, raise it in journal club rather than editing the digest directly, so the change is discussed before it lands.
Revision history
| 2026-02-25 | w.novak | Corrected a unit label in the second table — it read mg where it should have read mg/mL. |
| 2025-10-26 | compounding_ruth | Restructured into shorter sections so the outline navigation is usable. |
| 2025-10-02 | ppm_error | Split an overlong section in two and gave the second a proper heading. |
| 2025-07-28 | buffer_sheet | Reverted an unsourced change and asked the editor to re-apply it with a citation. |
| 2025-04-25 | KTurkington | Added cross-references to the two topics that most often ask this question. |
| 2024-12-10 | revision_history | Initial promotion from the source topic. Structure taken from the marked solution. |
Every edit to a maintained document records its author and a note explaining the change. An edit without a note may be reverted by any wiki editor under R9, and the revert is logged. Disagreements about content belong on the source topic rather than in the revision history (R10).
Related documents
- STEP 1 — trial digestSTEP 1 (N Engl J Med 2021): Does semaglutide 2.4 mg weekly reduce body weight in adults with obesity and no diabetes?
- STEP 2 — trial digestSTEP 2 (Lancet 2021): What weight reduction does semaglutide 2.4 mg achieve in people who also have type 2 diabetes?
- STEP 3 — trial digestSTEP 3 (JAMA 2021): What does semaglutide add on top of intensive behavioural therapy?
- STEP 4 — trial digestSTEP 4 (JAMA 2021): What happens if you stop after reaching the maintenance dose?
- SUSTAIN 6 — trial digestSUSTAIN 6 (N Engl J Med 2016): Is semaglutide cardiovascular-safe in high-risk type 2 diabetes, and is there benefit?