Abstract Body (Do not enter title and authors here):
Background: Heart failure (HF) and diabetes frequently co-exist, but whether worsening HF events are associated with dysglycemia and new-onset diabetes remains uncertain.

Aims: To explore glycemic trajectories before and after worsening HF events, the association between HF events and new-onset diabetes, and whether treatment benefits of finerenone on new-onset diabetes are mediated by reductions in HF events among persons with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) in the FINEARTS-HF trial.

Methods: FINEARTS-HF enrolled individuals with chronic HFmrEF/HFpEF, with or without diabetes. First, temporal trajectories of glycated hemoglobin (HbA_1c) were evaluated before and after HF events using repeated-measures linear regression and expressed using restricted cubic splines. Second, multivariable-adjusted Cox proportional hazards regression models were used to examine the rate of new-onset diabetes after (vs. before) worsening HF events. Third, whether reductions in HF events mediated the benefit of finerenone on new-onset diabetes was assessed.

Results: Among 6,001 FINEARTS-HF participants, 2,412 (40%) had a history of diabetes at baseline, of whom 1,671 (69%) had a diagnosis of diabetes that preceded HF and 741 (31%) had a diagnosis of diabetes either concurrent with or after HF. Overall, participants who experienced a worsening HF event (n=1,034) had higher HbA_1c levels compared with those who did not (P<0.001), and HbA_1c levels tended to increase slightly prior to HF events (Figure 1). Similar patterns were observed among participants with and without diabetes. The incidence of new-onset diabetes increased sharply after a HF event (Figure 2), with a >2-fold risk of new-onset diabetes after (vs. before) a worsening HF event (adjusted hazard ratio [HR], 2.61; 95% CI, 1.76-3.85). However, most (87%) new-onset diabetes events occurred before HF events or among participants without a HF event. Reductions in worsening HF with finerenone vs. placebo did not meaningfully attenuate the benefit of finerenone on new-onset diabetes (HR [95% CI] before and after adjustment for worsening HF events: 0.76 [0.59-0.97] and 0.77 [0.60-0.98], respectively).

Conclusions: Worsening HF events were associated with a substantially increased risk of new-onset diabetes in FINEARTS-HF, suggesting bidirectional interplay between HF and metabolic function. Benefits of finerenone on new-onset diabetes were independent of its benefits on worsening HF events.