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
- Diabetes Care 2022;45(4):888-897
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.
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.
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
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
- 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
- 1.00 EBAC
- Understand the SGLT2 inhibitor cardiovascular outcome trial (CVOT) data.
- Differentiate the latest guideline updates for the treatment of T2D and their recommendations regarding the importance of considering comorbidities, including atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF).
- Apply clinical and real-world evidence of the SGLT2 inhibitor class for use in prevention of hospitalisation in HF, as well as future ongoing studies in the treatment of HF.
- Assess the interrelationships linking diabetes, HF and CVD.
- Interpret the potential cardio-renal mechanisms of the SGLT2 inhibitor class in reducing the risk of CV, including HF.
- Evaluate emerging data of the treatment of HF with SGLT2 inhibitors in patients with or without T2DM.
- 1.00 EBAC
- Describe the evidence to support the use of renal denervation as a treatment modality in patients with resistant hypertension
- Understand renal denervation and how effective it is as a treatment option
- Identify patients with resistant hypertension suitable for renal denervation
- 1.00 EBAC
- Understand the SGLT2 inhibitor cardiovascular outcome trial (CVOT) data;
- differentiate the latest guideline updates for the treatment of T2D and their recommendations regarding the importance of considering comorbidities, including atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF);
- apply clinical and real-world evidence of the SGLT2 inhibitor class for use in prevention of hospitalisation in HF, as well as future ongoing studies in the treatment of HF;
- assess the interrelationships linking diabetes, HF and CVD;
- interpret the potential cardio-renal mechanisms of the SGLT2 inhibitor class in reducing the risk of CV, including HF. Evaluate emerging data of the treatment of HF with SGLT2 inhibitors in patients with or without T2DM.
- 1.00 (EBAC)
- Recall recent changes to guidelines following the publication of Phase III data with SGLT2 inhibitors in patients with HFrEF, with and without type 2 diabetes
- Describe the type and extent of clinical benefit observed when SGLT2 inhibitors are added to standard HF therapy in patients with HFrEF
- Assimilate prevailing hypotheses and insights from key thought leaders on optimal therapeutic sequencing of the ‘five pillars’ of HF therapy
- Apply newly gained knowledge on therapeutic sequencing to surrogate patient cases
- 0.25 AMA PRA Category 1 Credit™
- Recall the efficacy and safety of existing HCM treatments
- Summarize results from ongoing trials with experimental treatments for HFrEF and HCM