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FLOW: the kidney trial that stopped early

A 24 per cent reduction in major kidney events, with every secondary outcome agreeing. The dose was 1.0 mg — the diabetes dose, not the one sold for weight loss.

Dana Sullivan6 min read
FLOW: hazard ratios against placebo1.0Major kidney events0.76Cardiovascular death0.71Major cardiac events0.82Death from any cause0.80

FLOW is the trial that stopped early because it was working. It randomized 3,533 people with type 2 diabetes and chronic kidney disease to semaglutide 1.0 mg weekly or placebo, and an interim analysis recommended cessation before the planned end, after a median follow-up of 3.4 years [1]. The result is one of the strongest in this drug class, and it comes with a condition almost nobody mentions when quoting it — a condition that matters before you compare what any seller charges.

What it found

The primary outcome was a composite of kidney failure, a 50 per cent or greater fall in eGFR, or death from kidney or cardiovascular causes. Risk was 24 per cent lower on semaglutide, at 331 first events against 410, a hazard ratio of 0.76 (95% CI 0.66 to 0.88, P = 0.0003).

Every confirmatory secondary outcome moved the same way. The kidney-specific composite was 0.79 (95% CI 0.66 to 0.94). Death from cardiovascular causes was 0.71 (95% CI 0.56 to 0.89). Major cardiovascular events were 18 per cent lower at 0.82 (95% CI 0.68 to 0.98), and death from any cause 20 per cent lower at 0.80 (95% CI 0.67 to 0.95). The mean annual eGFR slope was less steep by 1.16 ml per minute per 1.73 m². Serious adverse events were reported in fewer participants on the drug than on placebo, 49.6 per cent against 53.8.

The condition on all of it

The dose was 1.0 mg weekly. That is the type 2 diabetes dose, and it is not the 2.4 mg weight-management dose that most compounded semaglutide sold online is titrated toward. The population was people with diabetes and established kidney disease, defined by specific eGFR and albumin-to-creatinine thresholds — not a general weight-loss population.

None of that makes the result less real. It means the result belongs to a drug at a dose in a population, and moving it onto a different dose in a different population is an assumption rather than a finding. If a seller’s page cites kidney benefits, the question to ask is which trial and at what dose — and most sellers publish nothing about dose at all, which we have counted in who publishes a dose ladder.

Why early cessation is worth understanding

Stopping a trial early for benefit is the right thing to do for the participants and it systematically inflates effect estimates, because trials stop at a moment when the data happen to look good. The effect here is large, consistent across every secondary outcome, and prespecified — which is about as reassuring as an early stop gets. It is still a reason to expect the real-world effect to be somewhat smaller.

For anyone with kidney disease considering a telehealth purchase, the practical gap is not the evidence. It is that this is a condition requiring monitoring, and most of the sellers tracked here publish nothing about who reviews a case or how often — a census we keep in what sellers publish and in what they will not tell you.

Frequently asked

How much did semaglutide reduce kidney events?
By 24 per cent against placebo — 331 first events against 410, a hazard ratio of 0.76 (95% CI 0.66 to 0.88) over a median 3.4 years.
Does this apply to the dose I would be sold?
Not directly. FLOW used 1.0 mg weekly, the type 2 diabetes dose. Most compounded semaglutide sold online is titrated toward the 2.4 mg weight-management dose.
Why did the trial stop early?
A prespecified interim analysis recommended cessation for benefit. That is correct for participants and it tends to inflate effect estimates, so expect the real-world effect to be somewhat smaller.

Sources

  1. [1] Perkovic V, et al. (2024). Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes New England Journal of Medicine. PMID 38785209

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