Summary:
In adults with type 2 diabetes and CKD (eGFR 25-75, UACR >100-5000 mg/g) on stable ACEi/ARB therapy, semaglutide 1.0 mg once weekly for median 3.4 years reduced primary composite kidney outcome (kidney failure, ≥50% eGFR decline, kidney/CV death) by 24% (HR 0.76, P<0.001), all-cause mortality by 20%, and CV events by 18% compared to matching placebo, with fewer serious adverse events (49.6% vs 53.8%) and trial stopped early for efficacy.
| PICO | Description |
|---|---|
| Population | Adults with T2D and CKD (eGFR 25-75, UACR >100-5000) on stable ACEi/ARB. |
| Intervention | Semaglutide 1.0 mg subcutaneous weekly for median 3.4 years. |
| Comparison | Matching placebo weekly for same duration. |
| Outcome | Kidney composite -24%. Mortality -20%. CV events -18%. Fewer serious AEs. Trial stopped early. |
Clinical Context
DKD affects ~40% of T2D patients. FLOW was the first dedicated kidney outcomes trial for a GLP-1 RA.
Clinical Pearls
1. First GLP-1 RA to Demonstrate Primary Kidney Endpoint Success: Elevates GLP-1 RAs to true kidney-protective agents.
2. Early Trial Termination for Efficacy: Reflects magnitude of kidney protection signal.
3. Benefits Across the CKD Spectrum: Enrolled patients with eGFR as low as 25.
4. Comprehensive Cardiorenal Protection: Simultaneous kidney, CV, and mortality benefits.
Practical Application
Consider semaglutide for T2D + CKD patients already on ACEi/ARB. No dose adjustment needed for kidney function. May complement SGLT2 inhibitors.
Study Limitations
Used 1.0 mg dose. SGLT2i use permitted but not mandated. Early termination limits long-term data.
Bottom Line
FLOW establishes semaglutide as first GLP-1 RA with primary kidney endpoint evidence: 24% kidney event reduction, 20% mortality reduction.
Source: Perkovic V, et al. “Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.” NEJM, 2024. Read article
