CONFIDENCE Data

Kerendia ▼ (Finerenone) in Type 2 Diabetes and Reduced Kidney Function: Efficacy and Safety Insights from CONFIDENCE Post-Hoc Analysis

Introduction

CONFIDENCE Trial Overview

CONFIDENCE was a randomized, double-blind, multicentre, factorial trial that evaluated the efficacy and safety of finerenone, empagliflozin, or their combination in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). The trial enrolled 818 patients with T2D, eGFR ≥30 mL/min/1.73 m², UACR ≥100mg/g, and receiving stable ACEi/ARB therapy. Participants were randomized to one of four arms: finerenone (10 or 20 mg daily), empagliflozin (10 mg daily), combination therapy, or placebo. The primary endpoint was change in UACR at 180 days, with key secondary endpoints including safety outcomes and changes in eGFR.

Post-Hoc Analyses Focus

This evidence summary presents two key post-hoc analyses from CONFIDENCE that specifically examined outcomes across different CKD stages:

1. JASN Post-Hoc Analysis (Mottl et al., 2025)
   : Evaluated the relationship between baseline kidney function and albuminuria reduction, with focus on eGFR <60 mL/min/1.73 m² subgroups and the impact of baseline eGFR on treatment response.

2. NDT KDIGO Risk Analysis (Vaduganathan et al., 2025)
   : Stratified outcomes by KDIGO risk categories, providing insights into efficacy and safety across risk groups that correspond to CKD stages 3a, 3b, and 4.

These analyses help inform clinical decision-making for patients with varying degrees of kidney function impairment within the licensed eGFR range.

KDIGO CKD Classification

According to the kidney disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline:

• Stage 3a
  : eGFR 45-59 mL/min/1.73 m² (mildly to moderately decreased kidney function)

• Stage 3b
  : eGFR 30-44 mL/min/1.73 m² (moderately to severely decreased kidney function)

• Stage 4
  : eGFR 15-29 mL/min/1.73 m² (severely decreased kidney function)

Key Efficacy Findings

Source: Adapted from Mottl et al., 2025 (Table 2).

Higher baseline eGFR was associated with greater albuminuria reduction:

Each 10 mL/min/1.73 m² higher baseline eGFR correlates with approximately 7 percentage points greater UACR reduction

This translates to patients with Stage 3a showing approximately 7 - 14 percentage points greater albuminuria reduction than Stage 3b patients

A fully adjusted model was fitted, and marginal means were computed for each level of baseline eGFR. The eGFR effect was computed by testing the joint probability of the baseline eGFR and baseline eGFR×visit interaction being different from 0 using a Wald test.

Source: Adapted from Vaduganathan et al., 2025.

Observations:

• All treatment arms demonstrated clinically meaningful reductions in albuminuria across KDIGO risk categories, with each achieving statistical significance versus baseline (All statistical analyses were performed using SAS and P < .05 was considered statistically significant.). 

• Combination therapy consistently provided the greatest albuminuria reduction in the very high-risk category

Source: Adapted from Mottl et al., 2025 (Table 4).

Source: Adapted from Vaduganathan et al., 2025 (Table 2).

• Hyperkalaemia risk increases with declining kidney function (Stage 3a < Stage 3b/4)
• Combination therapy showed numerically lower rates of hyperkalaemia with K⁺ >5.5 mmol/L compared to finerenone alone
• Early eGFR decline >30% was more common in patients with higher baseline eGFR
• Empagliflozin had lower rates of hyperkalaemia but similar rates of elevated serum K⁺ >5.5 mmol/L compared to finerenone in High-Risk patients

The CONFIDENCE trial data requires specific interpretation when evaluating outcomes across CKD stages:

1. Analytical framework
   : The JASN post-hoc analysis reports outcomes by composite eGFR thresholds (<60 vs ≥60 mL/min/1.73 m²) and albuminuria categories (<300 vs ≥300 mg/g), rather than by discrete CKD stages 3a, 3b, and 4.

2. eGFR-response relationship
   : A mixed-effects model established a quantitative relationship between baseline kidney function and treatment response, with approximately 7 percentage points greater UACR reduction per 10 mL/min/1.73 m² higher baseline eGFR, allowing for interpolation across the CKD continuum.

3. KDIGO risk stratification
   : The analyses utilized KDIGO risk categories that correspond to CKD stages—High risk generally aligning with Stage 3a and Very-High risk encompassing Stages 3b and 4—providing a structured approach to cross-stage interpretation.

4. Stage 4 representation
   : Patients with Stage 4 CKD (eGFR 15-29 mL/min/1.73 m²) are included within the Very-High risk category analyses but represent a smaller proportion of the study population compared to Stage 3a and 3b patients.

These methodological considerations provide context for clinicians when applying the CONFIDENCE findings across the spectrum of CKD stages within the licensed eGFR range of 25 to <60 mL/min/1.73 m².

1. These analyses represent post-hoc examinations with 180-day treatment duration; they were not powered to assess hard renal or cardiovascular outcomes

2. Stage-specific insights are derived from:

   • Mixed-effect models quantifying eGFR-dependent UACR response

   • KDIGO risk classification mapping that corresponds to CKD stages

3. Safety comparisons were descriptive and not adjusted for multiple comparisons

4. The sample size for Stage 4 CKD (eGFR 15-29 mL/min/1.73 m²) is smaller than for Stages 3a and 3b, limiting definitive conclusions specifically for this subgroup

5. Particular caution is warranted in Stage 4 CKD where hyperkalaemia risk may be further elevated, though findings remain consistent with SmPC recommendations

ACEi - Angiotensin-Converting Enzyme inhibitor

ARB - Angiotensin Receptor Blocker

CKD   Chronic Kidney Disease 

eGFR estimated Glomerular Filtration Rate 

JASN Journal of the American Society of Nephrology 

K⁺ Potassium 

KDIGO Kidney Disease: Improving Global Outcomes

NDT Nephrology Dialysis Transplantation 

OD Once Daily 

SmPC Summary of Product Characteristics 

T2D Type 2 Diabetes 

UACR Urine Albumin-to-Creatinine Ratio

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