Cardio-kidney-metabolic protective effects of semaglutide across the spectrum of chronic kidney disease

Table 2 Effects of semaglutide on kidney outcomes in the semaglutide use to Stabilize and Improve Glycemic Control in Individuals with Type 2 Diabetes, Evaluate Renal Function with Semaglutide Once Weekly, and Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity trials

Trial	Primary composite kidney endpoint	Effect of semaglutide on albuminuria	Composite kidney endpoint (Excl. albuminuria)	Effect of semaglutide on change in eGFR	Effect on ESKD
SUSTAIN-6	Reduced risk by 36% (HR: 0.64; 95%CI: 0.46-0.88; P = 0.005). Endpoint included macroalbuminuria, doubling of serum creatinine with eGFR ≤ 45, renal replacement, or renal death	New onset macroalbuminuria reduced by 46% (HR: 0.54, 95%CI: 0.37-0.77), P = 0.003 for semaglutide vs placebo	NR	Significant reduction in annual change in eGFR: Estimated treatment difference 06 mL/min/1.73 m2 (95%CI: 0.24-0.96, P = .001) Doubling of serum creatinine not reduced (HR: 1.28, 95%CI: 0.64-2.58)	No significant difference for semaglutide vs placebo, (HR: 0.91, 95%CI: 0.40-2.07)
FLOW	24% risk reduction (HR: 0.76; 95%CI: 0.66-0.88; P = 0.0003). Endpoint included kidney failure, ≥ 50% eGFR decline, or death from kidney/CV causes	Reduction of UACR ratio compared to placebo at week 104 to UACR at baseline (0.60 vs 0.88, HR: 0.68; 95%CI: 0.62-0.75) - significance not reached	24% risk reduction (same as primary endpoint; albuminuria not included)	Significant reduction in eGFR slope decline vs placebo (-2.19 vs -3.36 mL/min/1.73 m2 per year; between group difference, 1.16; 95%CI: 0.86-1.47; P < 0.001)	Semaglutide treated group reduced rate of persistent ≥ 50% reduction from baseline in eGFR (HR: 0.73; 95%CI: 0.59 to 0.89) and persistent eGFR < 15 mL/min/1.73 m2 (HR: 0.80; 95%CI: 0.61 to 1.06) - significance not reached
SELECT	22% reduction in composite endpoint (HR: 0.78; 95%CI: 0.64-0.95). Included eGFR < 15, ≥ 50% eGFR decline, renal death, dialysis, macroalbuminuria	Significant UACR reduction (P < 0.001)	18% risk reduction (HR 0.82; 95%CI 0.68-0.99) for endpoint excluding macroalbuminuria	Attenuated eGFR decline vs placebo at 104 weeks (-0.86 vs -1.61 mL/min/1.73 m2) with reduced eGFR slope decline in semaglutide treated group (-0.78 vs -1.17 mL/min/1.73 m2 per year (95%CI 0.3-0.48 P < 0.001)	Fewer ESKD events in semaglutide group however not significant due to low number of events

FLOW: Evaluate Renal Function with Semaglutide Once Weekly; SELECT: Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity; SUSTAIN-6: Semaglutide Use to Stabilize and Improve Glycemic Control in Individuals with Type 2 Diabetes; eGFR: Estimated glomerular filtration rate; UACR: Urinary albumin-creatinine ratio.