FLOW — trial digest
FLOW (N Engl J Med 2024): Does semaglutide reduce kidney disease progression and related death?
Citation and design
| Field | Value |
|---|---|
| Trial | FLOW |
| Intervention | Semaglutide 1.0 mg weekly |
| Publication | N Engl J Med, 2024 (first author Perkovic) |
| Design | Double-blind, placebo-controlled, stopped early for efficacy |
| Population | Adults with type 2 diabetes and chronic kidney disease |
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 reduce kidney disease progression and related death?
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
A kidney-outcome trial with a composite primary endpoint including sustained eGFR decline, kidney failure, and death from kidney or cardiovascular causes.
Stopped early for efficacy on the recommendation of the data monitoring committee.
Reading the composite component by component is essential, because the components differ in how patient-important they are.
Criticisms the journal club considered material
- Early stopping tends to produce effect estimates biased away from the null, and the confidence intervals should be read with that in mind.
- Background therapy included agents with their own renal benefit, so the result is an addition to contemporary care rather than a standalone effect.
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
| 2026-06-02 | coldchain_liu | Annual review: checked every figure against its source. Two rounded values tightened. |
| 2026-02-23 | k.brandl_de | Removed a paragraph that duplicated a linked page, and linked it instead. |
| 2025-12-14 | compounding_ruth | Updated a dated claim and added the date explicitly, per the maintenance convention. |
| 2025-11-01 | w.novak | Reverted an unsourced change and asked the editor to re-apply it with a citation. |
| 2025-06-13 | DSakamoto | Restructured into shorter sections so the outline navigation is usable. |
| 2025-02-20 | forest_plot | Split an overlong section in two and gave the second a proper heading. |
| 2024-11-28 | y.mensah | 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?
- STEP 8 — trial digestSTEP 8 (JAMA 2022): How does weekly semaglutide compare directly with daily liraglutide?