Source of FLOW trial

{{Infobox concept | name = FLOW trial | subtitle = Renal outcome trial | Drug = [[Semaglutide|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) }} '''FLOW''' was a randomised, double-blind, placebo-controlled trial of weekly [[Semaglutide|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.{{r|perkovic2024}} 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).{{r|perkovic2024}} 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]].{{r|perkovic2024}} == Design == 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.{{r|perkovic2024}} 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.{{r|lincoff2023}} 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.{{r|ich_e9}} == Results == | 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.{{r|perkovic2024}} 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.{{r|ich_e9}} == Interpretation == FLOW supports a renal benefit for semaglutide 1.0 mg in type 2 diabetes with chronic kidney disease, added to standard renal protection. It does not establish benefit in kidney disease without diabetes, at other doses, or for other members of the class.{{r|perkovic2024}} Together with [[SELECT trial|SELECT]] and [[LEADER trial|LEADER]]{{r|marso2016}} it forms the outcome evidence base for this molecule and its predecessor, and the pattern across those three — cardiovascular benefit in diabetes, cardiovascular benefit without diabetes, renal benefit in diabetic kidney disease — is what distinguishes an agent with outcome data from one with only intermediate endpoints.{{r|lincoff2023}} Whether the renal benefit is mediated by glycaemic control, weight, blood pressure, direct effects, or a combination is not established by the trial.{{r|perkovic2024}} == References == {{reflist}} <ref name="perkovic2024">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.</ref> <ref name="lincoff2023">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.</ref> <ref name="ich_e9">International Council for Harmonisation, ''E9(R1): Estimands and Sensitivity Analysis in Clinical Trials'' (2019).</ref> <ref name="marso2016">Marso SP, Daniels GH, Brown-Frandsen K, et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." ''New England Journal of Medicine'' 375(4):311–322 (2016). PMID 27295427.</ref> == See also == * [[Semaglutide]] * [[SELECT trial]] * [[LEADER trial]] * [[Surrogate endpoint]] {{DEFAULTSORT:FLOW trial}} [[Category:Renal outcome trials]] [[Category:Clinical evidence]] [[Category:Type 2 diabetes trials]]