Kidney and Survival Outcomes with Semaglutide by Chronic Kidney Disease Severity in the FLOW Trial

BACKGROUND: Semaglutide improved kidney and overall survival in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD) in the FLOW trial. The aim of the present analyses was to quantify these benefits across broad strata of CKD severity.

METHODS: FLOW was a double-blind, randomized, placebo-controlled trial (median follow-up 3.4 [interquartile range 2.9-4.0] years). Participants with T2D and estimated glomerular filtration rate (eGFR) 50-75 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) >300-<5000 mg/g, or eGFR 25-<50 mL/min/1.73 m2 and UACR >100-<5000 mg/g, were randomized to subcutaneous semaglutide 1 mg once-weekly or placebo. Subgroups were categorized by baseline eGFR (<30 to ≥60 mL/min/1.73 m2) or UACR (<100 to ≥2000 mg/g) to assess the primary outcome and individual components (≥50% eGFR decline, eGFR <15 mL/min/1.73 m2, dialysis, kidney transplant, and death due to kidney or cardiovascular causes), all-cause death, eGFR and UACR.

RESULTS: At baseline, mean±standard deviation eGFR was 47±15 mL/min/1.73 m2, and median (5th-95th percentile) UACR was 568 (51-3225) mg/g. The primary outcome occurred in 19% (331 out of 1767) versus 23% (410 out of 1766) with semaglutide treatment versus placebo (hazard ratio [HR] 0.76; 95% confidence interval [CI], 0.66-0.88). Death occurred in 13% (227 out of 1767) versus 16% (279 out of 1766), respectively (HR 0.80; 95% CI, 0.67-0.95). Across eGFR and UACR subgroups, HRs for the primary outcome remained consistent (P for interaction 0.83 and 0.42, respectively). For death, HRs were consistent among eGFR subgroups (P for interaction 0.54), but the HR was lowest (0.47; 95% CI, 0.31-0.70) for those with UACR ≥2000 mg/g (P for interaction 0.02). Estimated treatment effects on eGFR and UACR were generally consistent amongst subgroups.

CONCLUSIONS: Semaglutide reduced risks of major kidney disease events and all-cause death across wide-ranging categories of baseline eGFR and UACR, supporting semaglutide treatment in T2D throughout the spectrum of CKD severity represented in FLOW, including advanced CKD.