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Condition · Evidence Review

GLP-1 and Chronic Kidney Disease: FLOW Trial Results

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In May 2024, the FLOW trial showed semaglutide reduced the risk of major kidney disease events by 24% in adults with type 2 diabetes and chronic kidney disease. The trial was stopped early for efficacy. This is now the strongest renal outcome dataset for any non-SGLT2 inhibitor in diabetic kidney disease.

Key facts

  • FLOW trial: 3,533 adults with T2D and CKD (eGFR 25–75, UACR ≥100 mg/g). Semaglutide 1.0 mg vs placebo, median follow-up 3.4 years.
  • Primary result: 24% reduction in composite kidney outcome (HR 0.76, 95% CI 0.66–0.88).
  • Trial stopped early for efficacy in October 2023.
  • FDA renal indication: Pending review; expected 2026.

What FLOW actually tested

FLOW enrolled 3,533 adults with type 2 diabetes and chronic kidney disease (eGFR 25–75 mL/min/1.73 m² with significant albuminuria, or eGFR 50–75 with severe albuminuria). Participants were randomized to semaglutide 1.0 mg weekly or placebo, on top of standard renoprotective therapy (RAAS blockade, SGLT2 inhibitor allowed).

The composite primary endpoint was kidney failure, ≥50% reduction in eGFR, kidney death, or cardiovascular death. At a median 3.4 years of follow-up, the event rate was 18.7% with semaglutide vs 23.2% with placebo — a 24% relative risk reduction.

How this fits with SGLT2 inhibitors

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) are the cornerstone renoprotective therapy in T2D with CKD. FLOW participants were allowed to be on SGLT2 inhibitors; about 16% were at baseline. Subgroup analysis showed semaglutide benefit was present whether or not patients were on an SGLT2. This suggests additive — not redundant — renoprotection.

Mechanism in kidney disease

The renoprotective effect appears multifactorial: blood pressure reduction, improved glycemic control, weight loss, reduced inflammation, and possibly direct effects on glomerular hemodynamics. The eGFR slope (rate of decline) was slower in the semaglutide arm, consistent with disease modification rather than just acute hemodynamic effect.

Practical implications

For a patient with T2D and CKD already on an SGLT2 inhibitor and RAAS blockade, adding a GLP-1 (specifically semaglutide, where the trial-level evidence sits) is increasingly supported by guidelines. The 2024 KDIGO update reflects this.

Tirzepatide in kidney disease

Tirzepatide has not been tested at the FLOW scale in CKD. Secondary analyses from SURPASS trials show favorable effects on albuminuria, but a dedicated renal outcome trial does not exist. Until then, semaglutide remains the GLP-1 with the strongest CKD evidence base.

References

FLOW trial (Perkovic et al., NEJM 2024). See our research bibliography for full citation and additional renal sub-studies.