ADA 2021: Finerenone in the Chronic Kidney Disease and Diabetes Population

Finerenone is a mineralocorticoid receptor antagonist indicated for chronic kidney disease (CKD) with type 2 diabetes. Does the use of insulin affect its performance against kidney and cardiovascular issues?

The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study showed that finerenone reduces kidney and cardiovascular complications in patients with CKD and type 2 diabetes. In addition, the results demonstrated consistency independent of insulin use at baseline, and this area is the main focus of this subgroup analysis. The purpose of this analysis is to determine the amount of influence that insulin use has on kidney and cardiovascular outcomes and safety.

In this subgroup analysis of the FIDELIO-DKD trial, 5674 patients met the inclusion criteria to participate in the study and were randomized to either finerenone or placebo groups. Of those, 3637 patients were on insulin at baseline, while 2037 were not. In addition, the baseline characteristics had shown the duration of diabetes, history of cardiovascular disease, HbA1c, and Urine Albumin-to-Creatinine Ratio (UACR) were higher in patients using insulin than those who were not. The primary endpoint is the composite kidney outcome defined as time to kidney failure, ≥40% decrease in eGFR from baseline, or renal death. The secondary composite kidney outcome had the same criteria except for a ≥57% decrease in eGFR from baseline. Finally, the researchers defined composite cardiovascular outcome as the time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

The results for the primary composite kidney outcome had shown that patients with no baseline insulin use had a hazard ratio of 0.79 (95% CI: 0.64 to 0.96) when comparing finerenone use (n= 990) to placebo (n= 1047). Finerenone and placebo had similar cumulative incidence probabilities until the 12-month mark, and then the difference was apparent, with finerenone achieving a lower incidence probability than placebo to the 48-month mark. Similar findings had occurred in the insulin population, with a hazard ratio of 0.85 (95% CI: 0.73 to 0.98), and finerenone (n= 1843) having a lower cumulative incidence probability than placebo (n= 1794). The overall population hazard ratio for the primary composite kidney outcome was 0.82 (95% CI: 0.73 to 0.93) with a P-interaction of 0.56 between patients who used insulin and those who did not.

The secondary composite kidney outcome demonstrated insulin use had a hazard ratio of 0.77 (95% CI: 0.62 to 0.94), while no insulin use had 0.75 (95% CI: 0.57 to 1.00). The overall population hazard ratio was 0.76 (95% CI: 0.65 to 0.90) with a P-interaction of 0.93 between the two groups. The last endpoint was the composite cardiovascular outcome; insulin use had a hazard ratio of 0.82 (95% CI: 0.69 to 0.97), while patients with no insulin use had 0.95 (95% CI: 0.74 to 1.23). The overall population hazard ratio for cardiovascular outcome was 0.86 (95% CI: 0.75 to 0.99) and a P-interaction of 0.33 between insulin and no insulin use.

The change of UACR from baseline to the four-month mark demonstrated consistency regardless of insulin status as seen with an identical ratio of least squares-means of 0.68 with a P-Value <0.001 for both insulin and non-insulin use. The most common adverse effect was hyperkalemia, with finerenone users having the highest occurrence, as seen in 17% of patients using insulin compared to the 13.4% of patients with no insulin use. Serious adverse events were similar across all groups from 28.5% to 36.5%.

To summarize this subgroup analysis, finerenone had shown its capability to reduce kidney and cardiovascular outcomes regardless if the patient had used insulin or not. In addition, the safety profile was similar between both finerenone and placebo regardless of insulin use. A limitation of this study was the type of study this was since it was a subgroup analysis and relied on data gathered from the FIDELIO-DKD trial. Nevertheless, the clinical implication of this study is that finerenone is a practical option for patients with CKD and type 2 diabetes, whether they are on insulin or not.

Practice Pearls:

• Finerenone had shown effectiveness for kidney and cardiovascular outcomes.
• The most common side effect of finerenone was hyperkalemia, but adverse events were close among finerenone and placebo.
• The use of insulin did not make a difference in most subgroups when comparing finerenone to placebo.

Rossing, Peter et al. “405-P: Efficacy and Safety of Finerenone in Patients with CKD and T2D by Baseline Insulin Treatment.” American Diabetes Association 81^st Scientific Sessions. Diabetes, June 25, 2021

Bakris, George L et al. “Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.” The New England journal of medicine vol. 383,23 (2020): 2219-2229. doi:10.1056/NEJMoa2025845

Alan Martinez, PharmD Candidate, University of South Florida Taneja College of Pharmacy