Finerenone and SGLT2 Inhibitors Could Have Additive Effect on Kidney Protection

Conference | <b>American Diabetes Association</b>

Data from an analysis of FIDELIO-DKD suggests the renoprotective benefits of finerenone were consistent irrespective of SGLT2 inhibitor use and those using an SGLT2 inhibitor with finerenone resulted in greater UACR reductions.

Adding finerenone to treatment algorithms already containing an SGLT2 inhibitor could result in even greater renoprotective benefits, according to a new FIDELIO-DKD analysis.

Presented at the American Diabetes Association 81st Scientific Sessions (ADA 2021), the secondary analysis assessed the effect of finerenone according to background SGLT2 inhibitor use and found consistent benefit across all subgroups. Results also suggested patients using SGLT2 inhibitors had a greater UACR improvement than those not using SGLT2 inhibitors at baseline.

“What we see actually is that the effect seems to be additive, which seems to be in line with the concept that they work through different mechanisms. Where the SGLT2 inhibitors protect the kidney by hemodynamic actions and finerenone protects the kidney by preventing fibrosis and inflammation,” said Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at Steno Diabetes Center in Copenhagen, in an interview with Endocrinology Network, who cautioned against overinterpretation of results due to a small sample size.

With the recent revelations of SGLT2 inhibitors’ cardiorenal protective benefits an increased emphasis has been placed on the use of agents in the class. Add to this the growing excitement surrounding finerenone and the present analysis was among the most anticipated late-breaking abstracts from ADA 2021.

A randomized, double-blind, placebo-controlled trial enrolling 5674 patients with type 2 diabetes, a UACR from 30-5000 mg/g, an eGFR from 25-74 mL/min/1.73min2, and receiving optimized RAAS blockade, results of FIDELIO-DKD indicated use of finerenone was associated with a significantly reduced rate of the primary and secondary outcomes. Results of the study suggested finerenone use was associated with an 18% reduction in risk for progression of CKD and a 16% reduction in the composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

Of the 5673 included in FIDELIO-DKD, 259 (4.6%) were receiving an SGLT2 inhibitor at baseline. Investigators noted SGLT2 inhibitor use was initiated among 328 patients after the study began. Analysis based on use of SGLT2 inhibitors indicated results were consistent irrespective of use at baseline for the primary (P=.21) and secondary outcomes (P=.03).

Additionally, results suggested patients receiving finerenone had reductions in UACR without use of SGLT2 inhibitors (ratio of LS-means, 0.68; 95% CI, 0.65-0.71; P <.0001) but investigators also pointed out UACR reductions appeared to be greater among those using SGLT2 inhibitors at baseline (ratio of LS-means, 0.75; 95% CI, 0.62-0.90; P=.0024). Further analysis indicated treatment-emergent hyperkalemia events occurred less often in those using SGLT2 inhibitors compared to those not using an SGLT2 inhibitor.

For more on the results of this secondary analysis of FIDELIO-DKD, Endocrinology Network reached out to Rossing and that conversation is the subject of this ADA 2021 House Call.

This study, “Finerenone in Patients with CKD and T2D by SGLT2i Treatment: An Analysis of the FIDELIO-DKD Study,” was presented at ADA 2021.