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Disease Research December 2025 8 min read
Landmark Trial

FLOW Trial: Semaglutide Reduces Kidney Disease Progression by 24%

The first dedicated kidney outcomes trial with a GLP-1 drug was stopped early for overwhelming efficacy. Published in NEJM, the results could change treatment guidelines for millions.

The Bottom Line

In 3,533 patients with type 2 diabetes and chronic kidney disease, semaglutide reduced major kidney events by 24%, cardiovascular death by 29%, and all-cause mortality by 20% compared to placebo. The trial was stopped early because the benefits were clear. FDA review is underway.

Why This Trial Matters

Chronic kidney disease affects approximately 37 million Americans. Diabetes is the leading cause—about 40% of people with type 2 diabetes develop some degree of kidney disease. Once established, diabetic kidney disease progresses relentlessly toward dialysis or transplant, with dramatically elevated cardiovascular risk along the way.

FLOW (Evaluate Renal Function With Semaglutide Once Weekly) was the first trial designed specifically to test whether a GLP-1 receptor agonist could slow kidney disease progression and reduce kidney-related death.

Primary Endpoint Result

24%

Reduction in major kidney disease events (kidney failure, 50% eGFR decline, or death from kidney/cardiovascular causes)

The Numbers

3,533
Patients
3.4
Years Median Follow-up
331
Events (Semaglutide)
410
Events (Placebo)
Outcome Hazard Ratio Risk Reduction P-value
Primary composite (kidney events + CV death) 0.76 24% 0.0003
Kidney-specific events 0.79 21% —
Cardiovascular death 0.71 29% —
Major cardiovascular events (MACE) 0.82 18% 0.029
All-cause mortality 0.80 20% —

Stopped Early for Efficacy

FLOW was terminated early on recommendation of the independent data monitoring committee. At a prespecified interim analysis, the benefits were so clear that it would have been unethical to continue giving patients placebo.

"These are landmark findings and are likely to have a major impact on the management of CKD and type 2 diabetes. This is really one of the first trials that has shown convincing mortality benefits with any therapy in a target population of CKD and type 2 diabetes."

— Muthiah Vaduganathan, MD, Brigham and Women's Hospital

Who Was in the Trial

FLOW Enrollment Criteria

Included: Adults with type 2 diabetes AND chronic kidney disease (eGFR 25-75 mL/min/1.73m² with significant proteinuria)

Treatment: Semaglutide 1.0 mg once weekly (subcutaneous) vs placebo, on top of standard of care including ACE inhibitors/ARBs

Sites: 28 countries, ~400 investigator sites

Importantly, about 15% of patients were already on SGLT2 inhibitors (another class shown to protect kidneys). Semaglutide's benefits appeared consistent regardless of baseline SGLT2 inhibitor use, suggesting the drugs may be complementary.

How Semaglutide Protects Kidneys

Direct Effects

  • Reduces proteinuria (UACR)
  • Slows eGFR decline by 1.16 mL/min/year
  • Anti-inflammatory effects in kidney tissue
  • Reduces oxidative stress

Indirect Effects

  • Weight loss (~5.5 kg in FLOW)
  • Improved blood sugar control (-0.87% HbA1c)
  • Lower blood pressure (-3.79 mmHg systolic)
  • Cardiovascular risk reduction

The kidney-specific component of the primary endpoint showed a 21% reduction, indicating benefits beyond just reducing cardiovascular death.

Beyond Diabetic Kidney Disease

A separate 2024 trial tested semaglutide in patients with chronic kidney disease and obesity without diabetes. After 24 weeks:

Regulatory and Clinical Implications

Based on FLOW results, Novo Nordisk submitted a label extension application for Ozempic (semaglutide 1.0 mg) to include chronic kidney disease. FDA decision was anticipated in January 2025.

If approved, semaglutide would join SGLT2 inhibitors as the second class of drugs proven to slow diabetic kidney disease progression in dedicated outcomes trials.

"The findings from the FLOW trial have the potential to change the disease course of these high-risk patients and pave the way for new treatment strategies, offering hope to millions of patients globally."

— Richard E. Pratley, MD, AdventHealth Diabetes Institute, FLOW trial co-chair

Where Semaglutide Fits in Treatment

Current guidelines recommend SGLT2 inhibitors for diabetic kidney disease. The question now is whether to add semaglutide routinely, or reserve it for specific situations.

Notably, in patients already on SGLT2 inhibitors at baseline, the numerical benefit of adding semaglutide appeared smaller (though the interaction wasn't statistically significant due to small sample size). This will require further study.

Safety in Kidney Disease

A pooled analysis of semaglutide safety data in adults ≥65 years found the drug was well-tolerated. The most common issues were gastrointestinal (nausea, diarrhea, constipation)—consistent with the general GLP-1 RA profile.

No new safety signals emerged in the FLOW population despite more advanced kidney disease than previous semaglutide trials.

Primary Sources

Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Semaglutide is FDA-approved for type 2 diabetes and obesity. A label extension for chronic kidney disease is under regulatory review. Treatment decisions should be made with your healthcare provider.