FLOW trial: semaglutide slows kidney disease progression

Novo Nordisk announced headline results on March 6, 2024, from FLOW, a trial testing whether once-weekly injectable semaglutide 1.0 mg could protect the kidneys of people who have both type 2 diabetes and chronic kidney disease (CKD). The company said the trial was stopped early because the drug was working, and that it reduced the risk of kidney disease progression and of death from kidney or cardiovascular causes. The full text of that announcement was not accessible for this report ^[1].

The detailed numbers behind the announcement were published later in 2024 in the New England Journal of Medicine by Perkovic and colleagues on behalf of the FLOW trial committees and investigators ^[2]. In that publication, injectable semaglutide 1 mg in people with type 2 diabetes and CKD produced a significantly improved composite kidney outcome, with a hazard ratio of 0.76 ^[2]. A hazard ratio of 0.76 means the risk of the combined kidney outcome was about 24% lower in the semaglutide group than in the placebo group over the study period.

The trial's full name is FLOW, or Evaluate Renal Function with Semaglutide Once Weekly ^[2]. Other details from the original announcement — the number of participants, how long they were followed, the exact event counts, and the specific safety findings — are not contained in the sources available here, so they are not reported in this story.

How FLOW compares with the oral semaglutide trial

FLOW's kidney finding stands out because a later, much larger trial of the oral form of semaglutide did not repeat it. SOUL enrolled 9,650 people aged 50 or older with type 2 diabetes at high cardiovascular risk and randomized them to oral semaglutide up to 14 mg once daily or placebo, with median follow-up of roughly 48 to 49.5 months ^[2]. Oral semaglutide cut major adverse cardiovascular events by 14% — 12.0% of the semaglutide group versus 13.8% of the placebo group had a primary event, with a hazard ratio of 0.86 (95% CI 0.77–0.96; P=0.006) ^[2].

But SOUL's first confirmatory secondary outcome — major kidney disease events, a five-part composite including cardiovascular death, kidney death, a persistent drop in eGFR of 50% or more, persistent eGFR below 15 mL/min/1.73 m², or long-term dialysis or transplant — showed no difference between groups, and the statistical testing sequence stopped there ^[2]. The SOUL authors suggested the difference from FLOW might come from higher baseline kidney function (eGFR) in SOUL, the lower bioavailability of the oral formulation, or chance ^[2].

Why it matters for patients

For people living with both type 2 diabetes and CKD, FLOW addresses an outcome that matters in daily life: whether kidney function keeps declining toward dialysis or a transplant. The trial tested the 1.0 mg weekly injection, a dose used in type 2 diabetes care, not a weight-management dose ^[2].

The comparison with SOUL also carries a practical message. Commentary on the two trials notes that the FLOW kidney results cannot simply be extrapolated to daily oral semaglutide, because SOUL studied a different population with a different primary outcome and did not show a kidney benefit ^[2]. In other words, injectable and oral semaglutide performed similarly on cardiovascular events but not on kidney outcomes in these trials.

One limitation flagged by the SOUL authors applies broadly: trial populations at very high cardiovascular risk may not reflect everyone with type 2 diabetes, and SOUL enrolled only 28.9% women and 2.6% Black participants ^[2]. Whether FLOW had similar enrollment gaps is not stated in the available sources.

What happens next

FLOW's full results appeared in the New England Journal of Medicine in 2024 (volume 391, pages 109–21) ^[2]. SOUL was published in the same journal on March 29, 2025 ^[2]. Regulatory decisions and label changes tied to FLOW are not described in the sources available here.