However, the post-hoc analysis found a greater variability in HbA1c levels was associated with increased risk of cardiorenal outcomes.
New findings suggest risk reductions in cardiovascular and kidney outcomes with finerenone treatment in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) were not modified by baseline HbA1c, HbA1c variability, or duration of diabetes.
However, variability in HbA1c had associations with outcome risk, according to the findings.
“A greater variability in HbA1c, that is, the magnitude of the increase and decrease in HbA1c levels beyond ‘expected’ values over time (less-controlled disease), was associated with increased risks of cardiorenal outcomes,” wrote study author Janet B. McGill, MD, Washington University School of Medicine.
The late-breaking findings were presented at the American Diabetes Association (ADA) 2022 Scientific Sessions in New Orleans, Louisiana.
The results of the FIDELITY analysis of the FIDELIO-DKD and FIGARO-DKD studies found that finerenone reduced the risk of cardiovascular and kidney outcomes, without affecting HbA1c in the patient population. This post-hoc analysis of FIDELITY looked to evaluate the effect of finerenone by baseline HbA1c category and variability, as well as diabetes duration.
In FIDELITY, patients with T2D and CKD (UACR ≥30-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) were randomized to either finerenone or placebo. The effects of each cohort on cardiovascular (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline from baseline, or renal death) outcomes were analyzed using Cox proportional-hazards models.
A total of 13,026 patients were included in the analysis, with a mean baseline HbA1c of 7.7% and diabetes duration of 15.4 years. The patients were stratified by baseline HbA1c quartiles and diabetes duration quartiles:
Investigators noted those in higher baseline HbA1c quartiles had longer diabetes duration and more diabetes-related complications at baseline. They additionally found the proportion of females was higher compared to the other quartiles and these patients were more likely to have a higher UACR. Meanwhile, the history of cardiovascular disease was shown to be similar across the diabetes duration quartiles.
Data show risk reductions within the cardiovascular and kidney composite outcomes with finerenone compared to placebo were consistent across HbA1c (P-interaction, 0.52 and 0.09, respectively) and diabetes duration (P-interaction, 0.12 and 0.75, respectively) quartiles.
Within the overall population, greater HbA1c variability in the first year of treatment was found to be associated with higher cardiorenal risks. They saw each 1 unit increase in the mean absolute residual of HbA1c was associated with a 20% increased risk of cardiovascular event (hazard ratio [HR], 1.20; 95% CI, 1.07 - 1.35; P = .0016) and a 36% increased risk of a kidney event (HR, 1.36; 95% CI, 1.21 - 1.52; P <.001).
Moreover, the cardiovascular and kidney benefits of finerenone were not modified by HbA1c variability. Investigators observed treatment with finerenone was associated with a difference in probability of events at 3.5 years for cardiorenal outcomes, but this was found to be statistically non-significant (P-interaction, 0.48 and 0.09, respectively).
Regarding safety outcomes, investigators found the overall incidence of treatment-emergent adverse events were similar between the finerenone and placebo groups across the baseline HbA1c and diabetes duration quartiles.
They reported the incidence of treatment-emergent hyperkalemia was higher in patients treated with finerenone than placebo, while the highest incidence was observed in patients with the longest diabetes duration.
The study, “Effects of Finerenone in Patients with CKD and T2D are Independent of HbA1c at Baseline, HbA1c Variability and Duration of Diabetes,” was presented at ADA 2022.