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  • 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

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

What was known?

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.

Objective(s):

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

What this study adds:

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.

Clinical implications:

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.

Study design:

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.

Primary endpoints:

  • 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 Image removed.40% decrease in eGFR from baseline over at least 4 weeks; or renal death

Secondary endpoints:

  • 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

Inclusion criteria:

  • 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

Notable exclusion criteria:

  • 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

Findings:

  • 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

Interpretation:

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.

Limitations:

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

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