Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study

Abstract

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

Diversity, Equity, and Inclusion in Clinical Research: A Path Toward Precision Health for Everyone

“…9 This is an area with pressing unmet needs for a diverse population where minority groups bear a disproportionate burden. Yet, while an ideal estimate of representation in CKD clinical trials would suggest 35% as an enrollment target for Black or African American participants, 16 a survey of clinical studies reported in 2022 indicates most trials stand below that estimate, ranging between 5% and 29%, [17][18][19][20][21][22][23][24] and only one report showed 58.8% of African American participants. 25 This situation warrants a push for more inclusive research.…”

Cardiorenal benefits of finerenone: protecting kidney and heart

“…After a mean follow-up of 2.6 years, relative to placebo, finerenone significantly reduced CKD progression (primary endpoint) by 18% (HR 0.82; 95% CI = 0.7–0.93; p = 0.001], and decreased the composite secondary endpoint (death from CV causes, non-fatal myocardial infarction, nonfatal stroke, or hospitalization for HF) by 14% (HR 0.86; 95% CI = 0.75–0.99) ( Table 3 ). The benefit of finerenone was independent of the history of CV disease [ 11 ], blood pressure [ 49 ] and HbA1c [ 50 ] levels, as well as the use of insulin [ 50 ], SGLT2 inhibitors [ 51 ] or glucagon-like peptide receptor type 1 (GLP1) agonists [ 52 ]. In a secondary analysis of the FIDELIO-DKD trial, finerenone reduced the risk of newly diagnosed atrial fibrillation/flutter compared with placebo (3.2% vs 4.5%; p = 0.016) [ 53 ].…”

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management

“…Different trials also demonstrated a significant reduction in the primary outcome (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for HF) in those subjects with T2DM and chronic kidney disease receiving finerenone [ 98 – 100 ]. Indeed, finerenone significantly improved cardiorenal outcomes in patients with T2DM and kidney disease irrespective of HbA1c levels or insulin use [ 101 ]. Therefore, finerenone should be considered for treatment of patients with T2DM, and this agent is likely to be included as an important treatment option in future updates of current guidelines.…”