Mineralocorticoid receptor antagonists (MRAs) increase serum potassium. Finerenone—a nonsteroidal selective MRA—increased serum potassium and hyperkalemia events compared with placebo in the pivotal phase III study FIDELIO-DKD.

In this secondary model-based analyses, the dose–exposure–response relationship for serum potassium was quantified. The analyses demonstrated and explained a titration paradox, where higher finerenone doses were associated with lower serum potassium levels and lower incidences of hyperkalemia, based on serum potassium-guided dose adaption.

The impact of modified serum potassium inclusion and titration thresholds were simulated. The analyses demonstrated the effectiveness of finerenone dose personalization, supporting a favorable benefit–risk assessment and safe use in patients with chronic kidney disease and type 2 diabetes mellitus when guidance for dose and dose modification is followed.