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

Available evidence suggest that glycemic control influences the kidney outcomes in patients with type 2 diabetes (T2D) and mild chronic kidney disease (CKD), but data from large trials in patients with moderate to severe CKD and T2D is lacking. In the FIDELIO-DKD trial, finerenone reduced the risk of adverse cardiovascular (CV) and kidney events but the role of baseline glycemic control on treatment benefits of finerenone is not determined.

This subgroup analysis of FIDELIO-DKD investigated whether baseline haemoglobin A1c (HbA1c) level and insulin treatment influenced the previously reported benefits of finerenone.

The data from this secondary analysis of a large phase 3 trial suggests that finerenone protects the kidneys and CV system in patients with T2D and advanced CKD regardless of baseline HbA1c level or insulin use.

Unlike other approved therapies aiming to reduce kidney and CV risk, finerenone appears to delay  CKD progression and improve CV outcomes regardless of glycemic control – highlighting an important progress in treatment for patients with CKD and T2D.

In a subgroup analysis of FIDELIO-DKD, a multicentre, randomised, double-blind, placebo- controlled, parallel-group, event driven phase 3 trial (NCT02540993), patients were randomly assigned (1:1) to receive once-daily finerenone (10 or 20 mg) or matched placebo.

• Composite of time to kidney failure, defined as chronic dialysis for >90 days, kidney transplantation, or a sustained estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 confirmed after at least 4 weeks; a sustained ≥40% decrease in eGFR from baseline over at least 4 weeks; or renal death

• Composite of time to first onset of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalisation for heart failure
• Composite of kidney failure, a sustained ≥57% decrease in eGFR from baseline (for ≥4 weeks), or renal death

• Aged ≥18 years
• Clinically diagnosed T2D with
  • moderately elevated albuminuria, an estimated glomerular filtration rate (eGFR) of 25 to <60 mL/min/1.73 m2, and a history of diabetic retinopathy
  • or severely elevated albuminuria and an eGFR of 25 to <75 mL/min/1.73 m2
• On a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks prior to the screening visit
• Serum potassium level ≤4.8 mmol/L at the run-in and screening visits

• HbA1c >12% at screening
• Known nondiabetic kidney disease
• Chronic symptomatic heart failure with reduced ejection fraction (New York Heart Association class II–IV)
• Recent history of dialysis for acute kidney failure or a kidney transplant
• Uncontrolled hypertension

• Overall, 64.1% received insulin at baseline. Of 5,663 patients included in this analysis, 49.3% had baseline HbA1c <7.5% (58 mmol/mol)
• Median follow-up time was 2.6 years
• Treatment with finerenone, independent of baseline HbA1c level and insulin use, significantly reduced the kidney composite outcome   (Pinteraction = 0.41) and Cardiovascular composite outcome incidence (Pinteraction = 0.56)
• Baseline HbA1c level did not affect kidney event risk, however cardiovascular risk increased with higher HbA1c level
• Adverse events were similar between treatment arms regardless of basline parameters

According to these results, the kidney and CV benefits of finerenone remain irrespective of baseline HbA1c level or insulin use. These findings expand on prior analyses from FIDELIO-DKD that showed that finerenone benefits are also independent of baseline sodium-glucose Cotransporter 2 Inhibitors or glucagon-like peptide 1 receptor agonist use.

• Patients were not stratified according to baseline insulin use or HbA1c level
• Changes in treatment for diabetes were permitted during the study