Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 29:dc250472.
doi: 10.2337/dc25-0472. Online ahead of print.

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

Peter Rossing  1   2 , George Bakris  3 , Vlado Perkovic  4 , Richard Pratley  5 , Katherine R Tuttle  6   7 , Kenneth W Mahaffey  8 , Thomas Idorn  9 , Nicolas Belmar  9 , Heidrun Bosch-Traberg  9 , Søren Rasmussen  9 , Robert S Busch  10 , Ronald E Schmieder  11 , Pieter Gillard  12 , Johannes F E Mann  11   13 ; FLOW Investigator Group
Collaborators, Affiliations

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

Peter Rossing et al. Diabetes Care. .

Abstract

Objective: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide 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 persistent ≥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 baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile 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.

PubMed Disclaimer

Grants and funding