FLOW trial (revision 13)
Old revision·23:35, 21 Mar 2025·SurpassSunniva
| FLOW trialRenal outcome trial | |
|---|---|
| Drug | Semaglutide 1.0 mg weekly |
| Population | Type 2 diabetes with chronic kidney disease |
| Participants | 3,533 |
| Primary result | Kidney outcome HR 0.76 (95% CI 0.66–0.88) |
| Topic infobox · conventions | |
FLOW was a randomised, double-blind, placebo-controlled trial of weekly semaglutide 1.0 mg in 3,533 adults with type 2 diabetes and chronic kidney disease. It was stopped early for efficacy on the recommendation of its data monitoring committee.[1]
The primary composite comprised onset of kidney failure, a sustained fall of at least 50% in estimated glomerular filtration rate, or death from kidney or cardiovascular causes. It occurred less often on semaglutide, hazard ratio 0.76 (95% CI 0.66–0.88).[1]
The trial is significant because its endpoints are hard rather than surrogate: kidney failure and sustained loss of filtration function, not albuminuria alone. See Surrogate endpoint.[1]
Design
[edit]Participants had type 2 diabetes with an estimated glomerular filtration rate and albumin-to-creatinine ratio within defined ranges, and were on maximum tolerated renin–angiotensin system blockade. The trial therefore tested semaglutide added to established renal protection rather than in its place.[1]
The dose studied was 1.0 mg weekly — the type 2 diabetes dose, not the 2.4 mg obesity dose. As elsewhere in this field, results at one dose do not transfer to another.[2]
Early stopping for efficacy shortens follow-up and tends to produce effect estimates larger than the trial would have produced had it run to completion. This is a well-characterised property of stopping rules rather than a defect of any particular trial.[3]
Results
[edit]| Endpoint | Direction |
|---|---|
| Primary kidney composite | Reduced, HR 0.76 (0.66–0.88) |
| Annual eGFR slope | Less steep decline on semaglutide |
| Major adverse cardiovascular events | Reduced |
| Death from any cause | Reduced |
The estimated glomerular filtration rate slope is informative because it describes trajectory rather than a threshold crossing, and is less sensitive to the timing of individual events.[1]
An initial dip in filtration rate after starting is expected with several renoprotective therapies and reflects haemodynamic change rather than injury; interpreting an early fall as harm is a common error, and trials of this kind pre-specify the analysis to account for it.[3]
See also
References
- ^ a b c d e Perkovic V, Tuttle KR, Rossing P, et al. "Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes." New England Journal of Medicine 391(2):109–121 (2024). DOI:10.1056/NEJMoa2403347. PMID 38785209.
- ^ Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." New England Journal of Medicine 389(24):2221–2232 (2023). PMID 37952131.
- ^ a b International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).