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

Jul 29, 2025Diabetes care

Semaglutide's effects with or without mineralocorticoid receptor blockers in people with type 2 diabetes and chronic kidney disease

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Abstract

Semaglutide reduced the risk of the primary kidney outcome by 49% in people with type 2 diabetes and chronic kidney disease.

The primary kidney outcome included a significant reduction in persistent eGFR decline, kidney failure, or death from kidney or cardiovascular causes.
In individuals using mineralocorticoid receptor antagonists, semaglutide had a hazard ratio of 0.51 for the primary kidney outcome, indicating a substantial reduction in risk.
Semaglutide also reduced the risk of major adverse cardiovascular events (MACE) and all-cause mortality without differences based on mineralocorticoid receptor antagonist use.
Albuminuria levels at 104 weeks decreased by 15% in MRA users and 33% in nonusers receiving semaglutide compared to placebo.
The decline in estimated glomerular filtration rate was similarly mitigated with semaglutide across both MRA and non-MRA subgroups.

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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.

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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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