FLOW showed semaglutide reduces major kidney events 24% in adults with T2D and CKD. Stopped early for efficacy. Establishes semaglutide alongside SGLT2 inhibitors as a renoprotective agent in T2D + CKD.

Trial design

FLOW (Perkovic et al., NEJM 2024) enrolled 3,533 adults with T2D and stage 2–4 CKD (eGFR 25–75 mL/min/1.73m² with elevated albuminuria). Randomized to semaglutide 1.0 mg weekly or placebo, on top of standard renoprotective therapy (ACE/ARB).

Results

Composite kidney endpoint: HR 0.76 (24% relative reduction).
Persistent ≥50% eGFR decline: HR 0.74.
Kidney failure (KRT or sustained eGFR <15): HR 0.80.
Kidney or CV death: HR 0.71.
All-cause mortality: HR 0.80.

Trial stopped early for efficacy. Median trial duration 3.4 years.

Mechanism

Beyond glycemic and weight effects, GLP-1 receptor agonists appear to have direct renoprotective effects: reduced glomerular hyperfiltration, reduced oxidative stress, anti-inflammatory effects on renal interstitium, BP reduction. Benefit appears additive to ACE/ARB and complementary to SGLT2 inhibitor.

Practical implications

For T2D + CKD, GLP-1 receptor agonist therapy is now guideline-aligned alongside ACE/ARB and SGLT2 inhibitor.
Combination GLP-1 + SGLT2 inhibitor is increasingly common and biologically complementary.
KDIGO 2024 guidelines now recommend GLP-1 receptor agonists in T2D + CKD.

What about CKD without diabetes?

FLOW was T2D-only. The FLOW-NoDM trial program is enrolling. Mechanism would suggest benefit; trial evidence is forthcoming.

Dose consideration

FLOW used semaglutide 1.0 mg weekly — not the 2.4 mg used for weight indications. Some compounded programs default to titrations targeting weight loss endpoints; patients with CKD-directed treatment goals should discuss target dose with their prescriber.

See our detailed kidney disease page.