Ziyan Zhou, Linghua Fu, Dan Chen, Peng Yu, Gaosi Xu, Qinghua Wu, Tao Wu, Pingping Yang
SGLT2i showed the broadest cardiorenal benefits, while finerenone and semaglutide provided additional protection across selected outcomes. Finerenone increased hyperkalaemia and treatment discontinuation. The efficacy of finerenone-SGLT2i combination therapy requires further investigation.
AIM: To compare the cardiorenal efficacy and safety of finerenone, sodium-glucose cotransporter 2 inhibitors (SGLT2i), semaglutide and finerenone-SGLT2i combination therapy in diabetic kidney disease (DKD).
MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched through July 9, 2026 for randomized trials involving adults with Type 2 diabetes and DKD. A frequentist network meta-analysis estimated risk ratios (RRs) with 95% confidence intervals (CIs) for cardiorenal and safety outcomes.
RESULTS: Ten randomized datasets involving 37 923 participants were included. Compared with control, dapagliflozin, canagliflozin, finerenone and semaglutide reduced both cardiovascular composite events and composite kidney outcomes; sotagliflozin reduced cardiovascular composite events, and empagliflozin reduced composite kidney outcomes. SGLT2i showed the broadest overall pattern of benefit across cardiorenal outcomes. Dapagliflozin was associated with a lower risk of the composite kidney outcome than semaglutide (RR 0.71, 95% CI: 0.53-0.94), while most other efficacy comparisons between active monotherapies were not statistically significant. Finerenone increased hyperkalaemia (RR 2.03, 95% CI: 1.82-2.26) and treatment discontinuation due to adverse events (RR 1.18, 95% CI: 1.02-1.35). Finerenone plus empagliflozin was associated with a higher risk of hyperkalaemia than empagliflozin alone (RR 2.48, 95% CI: 1.22-5.06).
CONCLUSIONS: SGLT2i showed the broadest cardiorenal benefits, while finerenone and semaglutide provided additional protection across selected outcomes. Finerenone increased hyperkalaemia and treatment discontinuation. The efficacy of finerenone-SGLT2i combination therapy requires further investigation.