Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial

Mahaffey KW, Tuttle KR, Arici M, Baeres FM, Bakris G, Charytan DM, Cherney DZ, Chernin G, Correa-Rotter R, Gumprecht J, Idorn T, Pugliese G, Rasmussen IKB, Rasmussen S, Rossing P, Sokareva E, Mann JF, Perkovic V, Pratley R (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 46

Pages Range: 1096-1108

Journal Issue: 12

DOI: 10.1093/eurheartj/ehae613

Abstract

BACKGROUND AND AIMS: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. METHODS: Participants were randomized to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorized by estimated glomerular filtration rate < or ≥60 mL/min/1.73 m2, urine albumin-to-creatinine ratio < or ≥300 mg/g, or Kidney Disease Improving Global Outcomes (KDIGO) risk classification. RESULTS: Three thousand, five hundred and thirty-three participants were randomized with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.8%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% [hazard ratio (HR) 0.82 (95% confidence interval 0.68-0.98); P = .03], with consistency across estimated glomerular filtration rate categories, urine albumin-to-creatinine ratio levels, and KDIGO risk classification (all P-interaction > .13). Death due to any cause was reduced by 20% [HR 0.80 (0.67-0.95); P = .01], with consistency across estimated glomerular filtration rate categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by urine albumin-to-creatinine ratio was .01 [<300 mg/g HR 1.17 (0.83-1.65); ≥300 mg/g HR 0.70 (0.57-0.85)]. CONCLUSIONS: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with type 2 diabetes.

Involved external institutions

Stanford University United States (USA) (US) University of Washington United States (USA) (US) Hacettepe University Turkey (TR) Novo Nordisk A/S Denmark (DK) New York University (NYU) United States (USA) (US) University of Toronto Canada (CA) Hebrew University of Jerusalem Israel (IL) Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico (MX) Medical University of Silesia in Katowice / Śląski Uniwersytet Medyczny w Katowicach (SUM) Poland (PL) Università degli studi "La Sapienza" Italy (IT) Steno Diabetes Center Denmark (DK) LMU Klinikum Germany (DE) University of New South Wales (UNSW) Australia (AU) AdventHealth United States (USA) (US)

How to cite

APA:

Mahaffey, K.W., Tuttle, K.R., Arici, M., Baeres, F.M., Bakris, G., Charytan, D.M.,... Pratley, R. (2025). Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial. European Heart Journal, 46(12), 1096-1108. https://doi.org/10.1093/eurheartj/ehae613

MLA:

Mahaffey, Kenneth W., et al. "Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial." European Heart Journal 46.12 (2025): 1096-1108.

BibTeX: Download