GLP-1 Receptor Agonists Protect Kidneys and Reduce Mortality in CKD: Study
Chronic Kidney Disease
USA: A secondary analysis of the FLOW trial found that glucagon-like peptide-1 (GLP-1) receptor agonist therapy significantly reduced kidney-related events and mortality in patients with type 2 diabetes and chronic kidney disease (CKD). Importantly, these benefits were observed regardless of whether patients had established atherosclerotic cardiovascular disease (ASCVD) or were at high cardiovascular risk, supporting the broad use of GLP-1 receptor agonists in this population.
The findings were published in the Journal of the American College of Cardiology (JACC) by Katherine R. Tuttle, Division of Nephrology, University of Washington School of Medicine, Seattle, Washington, USA, and colleagues.
Patients with type 2 diabetes and chronic kidney disease (CKD) are at high risk of kidney disease progression, cardiovascular events, and premature death. While the FLOW trial previously demonstrated the kidney-protective effects of once-weekly semaglutide, it was unclear whether these benefits differed by baseline cardiovascular status. To investigate this, researchers analyzed outcomes according to the presence of ASCVD, heart failure, and overall cardiovascular risk.
The FLOW trial randomized adults with type 2 diabetes and CKD to receive either once-weekly semaglutide 1.0 mg or placebo. The primary outcome was a composite of major kidney events, including a ≥50% decline in eGFR, kidney failure, dialysis, transplantation, or kidney- or cardiovascular-related death. All-cause mortality was assessed as a key secondary outcome.
Of the 3,533 participants, 33.9% had established ASCVD and 19.2% had heart failure at baseline. Among those without established cardiovascular disease, 66.5% were classified as having high cardiovascular risk based on a PREVENT score of at least 20%.
Key findings were as follows:
- Semaglutide reduced the risk of major kidney outcomes in patients with type 2 diabetes and CKD across all cardiovascular risk groups.
- Kidney benefits were consistent regardless of the presence of ASCVD, heart failure, or elevated cardiovascular risk.
- Baseline cardiovascular status did not significantly influence the kidney-protective effects of semaglutide.
- Semaglutide also reduced the risk of all-cause mortality across the examined subgroups.
- Mortality benefits were observed in both patients with established cardiovascular disease and those at high cardiovascular risk without documented cardiovascular disease.
- The number needed to treat over three years to prevent one major kidney outcome was 22 in patients with ASCVD, 13 in those with heart failure, and 17 in those with high cardiovascular risk.
The investigators noted that previous FLOW analyses had already demonstrated a 24% reduction in major kidney outcomes and a 20% reduction in all-cause mortality with semaglutide. The current subgroup analyses extend those findings by showing that the benefits are maintained across a broad range of cardiovascular risk profiles.
The authors concluded that semaglutide provides meaningful protection against kidney disease progression and premature death in patients with type 2 diabetes and CKD, regardless of the presence of ASCVD, heart failure, or high cardiovascular risk. These results support the use of semaglutide as an important therapeutic option for improving long-term outcomes in this high-risk patient population.
Reference:
Tuttle, K. R., Bakris, G. L., Baeres, F. M., Bang, C. N., Bax, W. A., Belmar, N., Musinga, D., Cherney, D. Z., Chernin, G., Lim, S. K., Mann, J. F., Perkovic, V., Pratley, R., Ridker, P. M., Rossing, P., Schmieder, R., Shamkhalova, M. S., Sreenivasamurthy, L., & Mahaffey, K. W. (2026). Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses. JACC, 87(21), 2996-3012. https://doi.org/10.1016/j.jacc.2026.02.5125
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