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

Objective: In FLOW, 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 due to 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 [136/121 semaglutide/placebo]) and non-use (n=3,276 [1631/1645]). 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; 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 non-users versus placebo (P-interaction=0.22). eGFR 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.