Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis.

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Rossing P., Bakris G., Perkovic V., Pratley R., Tuttle K. R., Mahaffey K. W., ...More

Diabetes care, vol.48, no.11, pp.1878-1887, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 48 Issue: 11
  • Publication Date: 2025
  • Doi Number: 10.2337/dc25-0472
  • Journal Name: Diabetes care
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Public Affairs Index, DIALNET, Nature Index
  • Page Numbers: pp.1878-1887
  • Open Archive Collection: AVESIS Open Access Collection
  • Ankara University Affiliated: Yes

Abstract

OBJECTIVE: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglu-tide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use.

RESEARCH DESIGN AND METHODS: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persis-tent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/ CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended.

RESULTS: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from base-line with semaglutide by 15% (95% CI −41, 31) in MRA users and 33% (26, 39) in non-users versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety pro-file of semaglutide was comparable between subgroups.

CONCLUSIONS: In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use.