Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: Both chronic kidney disease (CKD) and cardiovascular (CV) disease are common in persons with type 2 diabetes. The aim of this analysis was to assess the effects of semaglutide versus placebo on CKD outcomes in type 2 diabetes by CV status or risk at baseline.
Study Design and Methods: A double-blind, randomized (1:1) phase 3 trial.
Sample Size: N=3533.
Population Studied: FLOW included participants with type 2 diabetes and CKD (estimated glomerular filtration rate [eGFR] 50–75 mL/min/1.73 m² and urine albumin–creatinine ratio [UACR] >300–<5000 mg/g, or, eGFR 25–<50 mL/min/1.73 m² and UACR >100–<5000 mg/g). Analyses were based on participant categorization at baseline by prior myocardial infarction (MI), stroke, MI or stroke, peripheral artery disease (PAD), or total CV risk in those without CV disease at baseline (PREVENT score; <20%/≥20%).
Intervention(s): Subcutaneous semaglutide 1.0 mg weekly or placebo.
Power Calculations: Event driven and designed for 90% power to detect a 20% relative risk reduction for the primary kidney outcome. There were no specific power calculations for subgroup analyses, which were pre-specified except for the PREVENT analysis.
Primary Outcome: A composite of kidney failure (eGFR <15 mL/min/1.73m², dialysis, transplant), ≥50% eGFR decline from baseline, and kidney or CV death.
Outcomes: Participants were followed for a median of 3.4 years. Their mean age was 67 years; 30% were women; mean eGFR was 47.0 mL/min/1.73 m²; median UACR was 568 mg/g. Compared to placebo, semaglutide resulted in a 24% relative risk reduction in the primary kidney outcome (hazard ratio 0.76; 95% confidence interval 0.66, 0.88). Effects of semaglutide on the primary kidney outcome (Figure 1) and annual change in eGFR (Figure 2) were consistent across subgroups according to prior MI, stroke, MI or stroke, PAD, or total CV risk at baseline (all p-heterogeneity >0.17).
Conclusions: In the FLOW trial, the benefits of semaglutide on CKD outcomes in participants with type 2 diabetes were similar regardless of baseline CV status or risk.