Introduction and Objective: Hypokalemia is associated with adverse cardiovascular outcomes in heart failure (HF) and may impair insulin release and action. However, whether hypokalemia promotes incident diabetes in HF is uncertain. Methods: In this FINEARTS-HF analysis, we evaluated the association between time-updated serum potassium levels and new-onset diabetes, defined as ≥2 HbA1c measurements ≥6.5% or initiation of a non-SGLT2i glucose-lowering medication. We also examined whether time-updated potassium accounted for the benefit of finerenone on new-onset diabetes. Results: Among 6,001 participants, 3,224 (54%) did not have diabetes at baseline and were included (mean age 72 ± 10; 47% female; mean HbA1c, 5.7% ± 0.4%). Over a median follow-up of 2.7 years, lower time-updated serum potassium levels were significantly associated with new-onset diabetes after multivariable adjustment (hazard ratio HR per 0.5 mmol/L decrease, 1.19; 95% CI, 1.04-1.36; P=0.012) (Figure 1A). Treatment effects of finerenone on new-onset diabetes (HR, 0.76; 95% CI, 0.59-0.97) were partially attenuated after accounting for time-updated serum potassium levels (HR, 0.80; 95% CI, 0.62-1.03; 19.3% mediated) (Figure 1B). Conclusion: These findings extend understanding of the adverse health effects of hypokalemia in HF and suggest hypokalemia avoidance may have favorable metabolic effects. Benefits of finerenone on new-onset diabetes appear to be primarily mediated through potassium-independent pathways. Disclosure J. Ostrominski: Advisory Panel; Current; Corcept Therapeutics. H. Lu: Advisory Panel; Current; Boehringer Ingelheim International GmbH. Other - Travel expenses; Current; Bayer AG. Advisory Panel; Current; AstraZeneca. Other - Travel expenses; Ended; Cytokinetics Inc., Abbott. P. Jhund: Research Support; Ended; AstraZeneca. Speaker's Bureau; Current; AstraZeneca. Advisory Panel; Current; Novo Nordisk. Consultant; Current; Bayer AG. Research Support; Current; Analog Devices, Roche Diagnostics. A. Voors: Consultant; Current; Anacardio, AstraZeneca, Bayer AG. Research Support; Current; Bayer AG. Consultant; Ended; Boehringer Ingelheim International GmbH. Consultant; Current; Cardurion, Corteria, Eli Lilly and Company. Consultant; Ended; Merck Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Consultant; Current; QYSense, Ryarna, Salubris. M. Brinker: Employee; Current; Bayer AG. Other - pending patent for finerenone for treatment of patients with CKD and T1D; Current; Bayer AG. Stock/Shareholder; Current; Bayer AG. Y. De Sanctis: Employee; Current; Bayer AG. S.D. Solomon: Research Support; Current; Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cardior, Cytokinetics, Edgewise, BridgeBio, Gossamer, GSK, Ionis, Lilly, NIH/NHLBI, Novartis, NovoNordis. Consultant; Current; Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, Askbio, AstraZeneca, Bayer, BMS, Bridgebio, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantu. M. Vaduganathan: Other - research grant support, served on advisory boards, or had speaker engagements; Current; Alnylam Pharmaceuticals, American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, L, Novartis, Novo Nordisk, Pharmacosmos, Recordati, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Research Support; Current; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Galmed, Impulse Dynamics, Novartis, Occlutech, and Pharmacosmos. A. Scalise: None. L. Hofmeister: Employee; Current; Bayer AG.
Ostrominski et al. (Fri,) studied this question.