Effects of finerenone in people with chronic kidney disease and type 2 diabetes are independent of <scp>HbA1c</scp> at baseline, <scp>HbA1c</scp> variability, diabetes duration and insulin use at baseline

McGill, Janet B.; Agarwal, Rajiv; Anker, Stefan D.; Bakris, George L.; Filippatos, Gerasimos; Pitt, Bertram; Ruilope, Luis; Birkenfeld, Andreas L.; Caramori, M. Luiza; Brinker, Meike; Joseph, Amer; Lage, Andrea; Lawatscheck, Robert; Scott, Charlie; Rossing, Peter

doi:10.1111/dom.14999

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…The FIDELITY prespecified pooled analysis of both Phase 3 studies confirmed a significant relative risk reduction of 23% in the composite kidney endpoint with finerenone versus placebo, and of 14% in the composite cardiovascular endpoint, including a 22% relative risk reduction in HF‐related hospitalization 67 . Post‐hoc analyses showed that the efficacy of finerenone was not modified by baseline HbA1c, HbA1c variability, diabetes duration, baseline insulin use, or obesity 68,69 . Finerenone was well tolerated, with AEs, kidney‐related AEs, and serious AEs occurring at similar rates to placebo 67 .…”

Section: Clinical Evidence For Non‐steroidal Mineralocorticoid Recept...mentioning

confidence: 89%

“…67 Post-hoc analyses showed that the efficacy of finerenone was not modified by baseline HbA1c, HbA1c variability, diabetes duration, baseline insulin use, or obesity. 68,69 Finerenone was well tolerated, with AEs, kidney-related AEs, and serious AEs occurring at similar rates to placebo. 67 Hyperkalaemia was confirmed as the most notable treatment-related AE associated with finerenone (14% of patients), but the rate of hyperkalaemia-related discontinuation was relatively low (1.7%), indicating that it was manageable through serum potassium monitoring and dose adjustments.…”

Section: Finerenone Phase 3 Trialsmentioning

confidence: 92%

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Non‐steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Solis‐Herrera,

Triplitt

2023

Diabetes Obesity Metabolism

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Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is a major health challenge associated with a disproportionately high burden of end‐stage renal disease, cardiovascular disease and death. This review summarizes the rationale, clinical evidence and practical implementation for non‐steroidal mineralocorticoid receptor antagonists (nsMRAs), a drug class now approved and recommended for patients with T2D and CKD at risk of cardiorenal disease progression. Three nsMRAs (finerenone, esaxerenone and apararenone) have been evaluated but finerenone is currently the only approved nsMRA for this indication. Two large‐scale, placebo‐controlled, Phase 3 studies evaluated finerenone added to a maximally tolerated dose of an angiotensin‐converting enzyme inhibitor or an angiotensin II receptor blocker. Over >2 years of treatment, finerenone was associated with a significant reduction in composite endpoints of renal and cardiovascular outcomes versus placebo. Esaxerenone or apararenone have both shown significant improvements in albuminuria versus placebo. In general, nsMRAs were well tolerated. Hyperkalaemia was the most notable treatment‐related adverse event and could generally be managed through serum potassium monitoring and dose adjustments. The nsMRAs are now an important component of recommended treatment for CKD associated with T2D, providing a significant reduction in the risk of cardiorenal progression beyond what can be achieved with glucose and blood pressure control.

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Section: Clinical Evidence For Non‐steroidal Mineralocorticoid Recept...mentioning

confidence: 89%

Section: Finerenone Phase 3 Trialsmentioning

confidence: 92%

Non‐steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Solis‐Herrera,

Triplitt

2023

Diabetes Obesity Metabolism

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“…The FIDELITY study, which combined the FIGARO-DKD and FIDELIO-DKD studies, demonstrated an average of 36% reduction in UACR at 4 months and a significant reduction in the combined renal outcome (renal failure, >57% eGFR reduction, and renal disease-related death) (HR 0.77, p = 0.0002) [170]. The benefit on cardiorenal outcome was observed irrespective of the use of SGLT2is, glycemic control, and duration of diabetes in the FIDELITY cohort [171,172].…”

Section: Finerenonementioning

confidence: 96%

Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges

Fujii

Shibata

2023

IJMS

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Regulation and action of the mineralocorticoid receptor (MR) have been the focus of intensive research over the past 80 years. Genetic and physiological/biochemical analysis revealed how MR and the steroid hormone aldosterone integrate the responses of distinct tubular cells in the face of environmental perturbations and how their dysregulation compromises fluid homeostasis. In addition to these roles, the accumulation of data also provided unequivocal evidence that MR is involved in the pathophysiology of kidney diseases. Experimental studies delineated the diverse pathological consequences of MR overactivity and uncovered the multiple mechanisms that result in enhanced MR signaling. In parallel, clinical studies consistently demonstrated that MR blockade reduces albuminuria in patients with chronic kidney disease. Moreover, recent large-scale clinical studies using finerenone have provided evidence that the non-steroidal MR antagonist can retard the kidney disease progression in diabetic patients. In this article, we review experimental data demonstrating the critical importance of MR in mediating renal injury as well as clinical studies providing evidence on the renoprotective effects of MR blockade. We also discuss areas of future investigation, which include the benefit of non-steroidal MR antagonists in non-diabetic kidney disease patients, the identification of surrogate markers for MR signaling in the kidney, and the search for key downstream mediators whereby MR blockade confers renoprotection. Insights into these questions would help maximize the benefit of MR blockade in subjects with kidney diseases.

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“…Furthermore, some FIDELITY analyses emphasize the benefits of early treatment initiation and co-administration of potassium-binding agents to maximize the protective effects of FIN in individuals with DKD ( 100 , 103 ). FIN improved cardiorenal outcome in patients with DKD, regardless of baseline HbA1c ( 94 , 104 , 105 ), HbA1c variability ( 104 ), diabetes duration ( 104 ), baseline insulin use ( 104 , 105 ), baseline HF history ( 106 , 107 ), prevalent atherosclerotic CVD ( 108 ), and history of atrial fibrillation/flutter at baseline ( 96 ). Additionally, it is worth noting that the antihypertensive effect of adding FIN to a maximally tolerated dose of ACEI or ARB was relatively modest ( 87 , 88 ).…”

Section: Renal Protection Of Fin In Clinicmentioning

confidence: 99%

Overview of the safety, efficiency, and potential mechanisms of finerenone for diabetic kidney diseases

Chen,

Zheng,

Wang

et al. 2023

Front. Endocrinol.

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Diabetic kidney disease (DKD) is a common disorder with numerous severe clinical implications. Due to a high level of fibrosis and inflammation that contributes to renal and cardiovascular disease (CVD), existing treatments have not effectively mitigated residual risk for patients with DKD. Excess activation of mineralocorticoid receptors (MRs) plays a significant role in the progression of renal and CVD, mostly by stimulating fibrosis and inflammation. However, the application of traditional steroidal MR antagonists (MRAs) to DKD has been limited by adverse events. Finerenone (FIN), a third-generation non-steroidal selective MRA, has revealed anti-fibrotic and anti-inflammatory effects in pre-clinical studies. Current clinical trials, such as FIDELIO-DKD and FIGARO-DKD and their combined analysis FIDELITY, have elucidated that FIN reduces the kidney and CV composite outcomes and risk of hyperkalemia compared to traditional steroidal MRAs in patients with DKD. As a result, FIN should be regarded as one of the mainstays of treatment for patients with DKD. In this review, the safety, efficiency, and potential mechanisms of FIN treatment on the renal system in patients with DKD is reviewed.

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Effects of finerenone in people with chronic kidney disease and type 2 diabetes are independent of HbA1c at baseline, HbA1c variability, diabetes duration and insulin use at baseline

Cited by 5 publications

References 35 publications

Non‐steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Non‐steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges

Overview of the safety, efficiency, and potential mechanisms of finerenone for diabetic kidney diseases

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