STEP 2 — trial digest
STEP 2 (Lancet 2021): What weight reduction does semaglutide 2.4 mg achieve in people who also have type 2 diabetes?
Citation and design
| Field | Value |
|---|---|
| Trial | STEP 2 |
| Intervention | Semaglutide 2.4 mg and 1.0 mg weekly |
| Publication | Lancet, 2021 (first author Davies) |
| Design | Double-blind, placebo- and active-controlled, 68 weeks |
| Population | Adults with overweight or obesity and type 2 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
What weight reduction does semaglutide 2.4 mg achieve in people who also have type 2 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
Weight reduction in the diabetes population was consistently smaller than in STEP 1, which is a robust and reproducible observation across this class rather than a quirk of one trial.
Including a 1.0 mg arm allowed a within-trial dose comparison, which is more informative than comparing across trials.
Glycaemic improvement accompanied the weight change, as expected.
Criticisms the journal club considered material
- Background glucose-lowering therapy differed between participants and complicates attribution.
- The mechanism for the attenuated weight effect in diabetes is not established, and plausible explanations exist that the trial cannot distinguish.
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
| 2025-08-29 | sourced_claims | Corrected a unit label in the second table — it read mg where it should have read mg/mL. |
| 2025-04-13 | j.delacroix | Added the worked example that the review thread asked for. |
| 2025-03-04 | unit_conversion | Added cross-references to the two topics that most often ask this question. |
| 2024-12-26 | ms_holloway | 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 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?