STEP 1 — trial digest
STEP 1 (N Engl J Med 2021): Does semaglutide 2.4 mg weekly reduce body weight in adults with obesity and no diabetes?
Citation and design
| Field | Value |
|---|---|
| Trial | STEP 1 |
| Intervention | Semaglutide 2.4 mg weekly |
| Publication | N Engl J Med, 2021 (first author Wilding) |
| Design | Double-blind, placebo-controlled, 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
Does semaglutide 2.4 mg weekly reduce body weight in adults with obesity and no diabetes?
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 pivotal obesity trial for semaglutide and the reference point for almost every subsequent comparison in the class.
The magnitude of mean weight reduction was substantially larger than anything previously achieved pharmacologically in this population, which is why the trial changed the field rather than merely adding to it.
Discontinuation for gastrointestinal reasons was a meaningful minority and the profile was consistent with the rest of the class.
The trial was conducted with a lifestyle intervention in both arms, which means the placebo arm was not a no-treatment arm.
Criticisms the journal club considered material
- The estimand matters: results reported under a treatment-policy framing include people who stopped, and the number quoted in secondary coverage is frequently the one that does not.
- The enrolled population was narrower than the population now asking about the drug, particularly regarding baseline body mass index and comorbidity.
- 68 weeks is a long trial and a short exposure for a condition managed over decades.
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
| 2026-04-26 | titration_diary | Annual review: checked every figure against its source. Two rounded values tightened. |
| 2026-01-14 | NLoughran | Corrected a unit label in the second table — it read mg where it should have read mg/mL. |
| 2025-11-02 | dietitian_hollis | Added the worked example that the review thread asked for. |
| 2025-09-18 | outline_first | Added cross-references to the two topics that most often ask this question. |
| 2025-04-27 | mira.patel | Citation sweep: two references did not support the sentences attached to them and have been replaced. |
| 2025-01-02 | q.zhao_qa | 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 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?
- STEP 8 — trial digestSTEP 8 (JAMA 2022): How does weekly semaglutide compare directly with daily liraglutide?
- SUSTAIN 6 — trial digestSUSTAIN 6 (N Engl J Med 2016): Is semaglutide cardiovascular-safe in high-risk type 2 diabetes, and is there benefit?