FLOW Trial: Renal Benefits of Semaglutide in T2DM Similar Regardless of Baseline CV Risk

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By Lucas Marinacci on

Key Points

  • Both chronic kidney disease (CKD) and cardiovascular disease (CVD) are prevalent in type 2 diabetes (T2DM), contributing to morbidity and mortality.
  • The FLOW trial demonstrated that semaglutide, a GLP-1 receptor agonist, was associated with a 24% relative risk reduction in the primary composite kidney outcome compared to placebo among those with T2DM.
  • This analysis stratified by baseline CVD status and CVD risk, and found consistent renal benefits across these subgroups without evidence of a heterogeneous treatment effect.

CKD and CVD  are leading causes of death and disability in patients with T2DM. Both conditions often coexist, increasing the risk of adverse outcomes. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in improving glycemic control and reducing the risk of CV events, but its effects on CKD outcomes, particularly in subgroups defined by CVD risk, are less well understood.

On November 18th  2024, findings from “Benefits of Semaglutide on Chronic Kidney Disease Outcomes by Cardiovascular Status or Risk in the FLOW trial” were presented at AHA Scientific Sessions 2024.

The FLOW trial was a phase 3, double-blind, randomized controlled study designed to assess the effects of semaglutide on CKD progression in patients with type 2 diabetes. The study included 3,533 participants with type 2 diabetes and CKD, who were randomized to receive weekly subcutaneous semaglutide 1.0 mg or placebo. Participants met one of two inclusion criteria: eGFR 50–75 mL/min/1.73 m² with a urine albumin creatinine ratio (UACR) >300 to <5,000 mg/g, or eGFR 25–<50 mL/min/1.73 m² with a UACR >100 to <5,000 mg/g. Patients were followed for a median of 3.4 years. The trial’s primary endpoint was a composite of kidney failure (eGFR <15 mL/min/1.73 m², dialysis, or transplant), ≥50% eGFR decline from baseline, and kidney or CV death. This pre-specified subgroup analyses  stratified the participants by prior cardiovascular events or  CVD risk, including myocardial infarction (MI), stroke, peripheral artery disease (PAD) in those with baseline CVD, and CVD risk estimated using the PREVENT score in those without baseline CVD (categorized into <20% or ≥ 20%).

At baseline, participants had a mean age of 67 years, 30% were female, mean eGFR was 47 mL/min/1.73 m², and median UACR was 568 mg/g. In the overall population, semaglutide reduced the relative risk of the composite kidney outcome by 24% compared to placebo (HR: 0.76; 95% CI: 0.66–0.88). Annual eGFR decline was also slower with semaglutide. Benefits were consistent across all CVD and CV risk subgroups. Among those with prior MI, stroke, or PAD, hazard ratios ranged from 0.72 to 0.95, showing no significant heterogeneity. Patients with higher baseline CV risk (PREVENT score ≥20%) experienced similar reductions in kidney outcomes (HR: 0.73; 95% CI: 0.58–0.91) compared to those with lower risk scores (HR: 0.73; 95% CI: 0.49–1.08).

These FLOW trial results demonstrate that semaglutide provides substantial benefits in slowing CKD progression and reducing kidney failure in type 2 diabetes, regardless of cardiovascular status or risk. The findings underscore the broad applicability of semaglutide in managing the dual burden of diabetes and CKD.