Summary: In patients with type 2 diabetes and chronic kidney disease, once-weekly subcutaneous semaglutide 1.0 mg reduced the risk of a composite of major kidney disease events by 24 percent compared with placebo (hazard ratio 0.76; 95% CI 0.66 to 0.88; P = 0.0003) over a median follow-up of 3.4 years. Cardiovascular death, major cardiovascular events, and all-cause death were also reduced.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3533 adults with type 2 diabetes and chronic kidney disease (eGFR 25 to 75 ml/min/1.73 m² with urinary albumin-to-creatinine ratio >100 to <5000); double-blind, randomised, multinational trial (FLOW; NCT03819153). Funded by Novo Nordisk, the manufacturer. |
| Intervention | Subcutaneous semaglutide 1.0 mg once weekly (n = 1767). |
| Comparison | Matching placebo once weekly (n = 1766). |
| Outcome | Primary composite of major kidney disease events (kidney failure, ≥50% eGFR decline, or kidney-related or cardiovascular death): 331 vs 410 first events; HR 0.76 (95% CI 0.66 to 0.88; P = 0.0003), a 24% relative reduction. Death from cardiovascular causes: HR 0.71 (95% CI 0.56 to 0.89). Major adverse cardiovascular events: HR 0.82 (95% CI 0.68 to 0.98; P = 0.029). Death from any cause: HR 0.80 (95% CI 0.67 to 0.95; P = 0.01). Mean annual eGFR slope less steep by 1.16 ml/min/1.73 m² (P < 0.001). Serious adverse events: 49.6% (semaglutide) vs 53.8% (placebo). Absolute risk reduction and number needed to treat were not reported in the primary publication. |
Semaglutide and Kidney Outcomes (FLOW)
RCT · T2D + CKD · median 3.4 years
Once-weekly semaglutide cut major kidney disease events by 24% and reduced cardiovascular death, MACE, and all-cause mortality in type 2 diabetes with CKD.
Expert Commentary
The verdict is that this large, double-blind, placebo-controlled trial provides robust evidence that once-weekly semaglutide reduces clinically important kidney and cardiovascular outcomes in type 2 diabetes with established chronic kidney disease. The primary composite was reduced by 24 percent, and the benefit was supported by consistent, hierarchically tested reductions in cardiovascular death, major cardiovascular events, and all-cause mortality, with a less steep eGFR decline. The effect sizes are plausible and broadly aligned with the established cardiorenal class effect, and serious adverse events were not increased. Two cautions are warranted. The trial was funded by the manufacturer and was stopped early at a prespecified interim analysis, a design feature that can inflate the apparent magnitude of treatment effect; absolute risk reduction and number needed to treat were not reported, which limits direct translation to individual patients. Can I use this with my patients? Yes, in patients with type 2 diabetes and chronic kidney disease who meet the trial eligibility, particularly those with albuminuria and an eGFR in the 25 to 75 range, semaglutide is a reasonable addition to guideline-directed therapy. Clinicians should confirm tolerability and titrate gradually. Independent and longer-term data would further strengthen confidence in durability and safety.
References
Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347