FLOW trial (revision 9)

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]

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]