Summary: In the FLOW double-blind randomised trial of 3533 adults with type 2 diabetes and chronic kidney disease, once-weekly subcutaneous semaglutide 1.0 mg reduced the composite of major kidney disease events and kidney-or-cardiovascular death by 24% versus placebo (hazard ratio 0.76; 95% CI 0.66 to 0.88; P=0.0003) over a median 3.4 years. Cardiovascular death (HR 0.71) and all-cause death (HR 0.80) were also reduced.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3533 adults with type 2 diabetes and chronic kidney disease (eGFR 25 to 75 mL/min/1.73m2 with elevated urinary albumin-to-creatinine ratio); double-blind, randomised, multicentre trial (FLOW; NCT03819153); median follow-up 3.4 years. |
| Intervention | Once-weekly subcutaneous semaglutide 1.0 mg (n=1767). |
| Comparison | Matching placebo on top of standard care (n=1766). |
| Outcome | Primary composite (kidney failure, sustained >=50% eGFR decline, or kidney/cardiovascular death): 331 vs 410 first events; HR 0.76 (95% CI 0.66 to 0.88; P=0.0003), a 24% relative reduction. Kidney-specific composite: HR 0.79 (95% CI 0.66 to 0.94). Annual eGFR slope less steep by 1.16 mL/min/1.73m2 (P<0.001). Cardiovascular death: 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). All-cause death: HR 0.80 (95% CI 0.67 to 0.95; P=0.01). Serious adverse events were less frequent with semaglutide (49.6% vs 53.8%). |
Semaglutide in Diabetic Kidney Disease (FLOW)
RCT · type 2 diabetes + CKD · 3.4 years
Once-weekly semaglutide cut the risk of major kidney disease events and kidney or cardiovascular death by 24% in type 2 diabetes with chronic kidney disease, with parallel reductions in cardiovascular and all-cause mortality.
Expert Commentary
This is a positive, adequately powered phase 3 trial that establishes a kidney-protective role for semaglutide in type 2 diabetes with established chronic kidney disease. The 24% relative reduction in the primary composite was driven by clinically meaningful components, and the consistency across the kidney-specific outcome, eGFR slope, cardiovascular death, and all-cause mortality strengthens confidence that the signal is real rather than a statistical artefact. The double-blind, placebo-controlled design and the lower serious-adverse-event rate in the active arm are reassuring. Two cautions temper the enthusiasm. The trial was funded by the drug manufacturer, and it was stopped early at a prespecified interim analysis, a practice that can inflate the apparent magnitude of benefit, so the true effect size may be somewhat smaller than reported. Can I use this with my patients? Yes, for adults resembling the enrolled population, those with type 2 diabetes and an eGFR roughly 25 to 75 with albuminuria, semaglutide is a reasonable add-on to renin-angiotensin blockade and an SGLT2 inhibitor where tolerated. Clinicians should confirm renal eligibility, counsel on gastrointestinal effects, and titrate gradually. Wider uptake should follow as access and cost barriers ease.
References
Perkovic V, Tuttle KR, Rossing P, 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