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
Authors' conclusion
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.
Study context
- Population
- People with T2D and chronic kidney disease (CKD); baseline mineralocorticoid receptor antagonist (MRA) predominantly spironolactoneMRA users 257
- Comparison
- Once-weekly subcutaneous semaglutide 1.0 mg vs placebo, by baseline MRA use
- Primary endpoint
- Composite of:
- Time to first persistent ≥50% eGFR reduction from baseline
- Kidney failure
- Death from kidney/cardiovascular (CV) causes
Methodological detailssubgroup analysis by baseline MRA use
- Subgroup analysis by baseline MRA use
Primary result
As reported in the abstract
Primary kidney outcome by baseline MRA use
Semaglutide vs PlaceboHazard ratio (95% CI)P value
MRA users (n = 257: 136 semaglutide, 121 placebo); 59 events; risk reduced by 49%
0.51(0.30–0.86)
MRA nonusers (n = 3,276: 1,631 semaglutide, 1,645 placebo); 682 events; risk reduced by 21%
0.79(0.68–0.92)
P = 0.12for interactionFurther findings
Major adverse CV events (MACE) and all-cause mortality by MRA subgroup
- No heterogeneity, favoring semaglutide in both MRA subgroups
- P for interaction > 0.7
Albuminuria reduction from baseline, semaglutide vs placebo · 104 weeks
- MRA users: reduction
- 15% (95% CI −41, 31)
- Interaction
- P for interaction = 0.22
- Nonusers: reduction 33% (26, 39)
eGFR decline
- Similarly reduced with semaglutide in both subgroups
- P for interaction = 0.71
Safety
- Safety profile of semaglutide comparable between subgroups
Original publication
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. Diabetes Care. Published 29 July 2025. doi:10.
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