What diseases does Finerenone treat?

Introduction to Finerenone
Definition and Mechanism of Action
Finerenone is a novel, non‐steroidal mineralocorticoid receptor (MR) antagonist that distinguishes itself from traditional steroidal MRAs such as spironolactone and eplerenone through its high selectivity and binding affinity to the MR, along with minimal off‐target actions on androgen receptors, progesterone receptors, and glucocorticoid receptors. Its mechanism of action is based on blocking the deleterious effects of aldosterone and other mineralocorticoids on target organs. Overactivation of the MR is known to trigger inflammatory cascades and fibrosis in the cardiovascular and renal systems, which subsequently leads to structural and functional organ damage. By antagonizing the MR, finerenone blunts these inflammatory and fibrotic processes, thereby preserving the functional integrity of the heart and kidneys. This balanced distribution of finerenone in kidney and cardiac tissues—as demonstrated in preclinical studies where it showed equitable accumulation in both tissues—contributes to its robust cardiorenal protective effects, making it a promising agent in treating complex conditions where both the heart and kidneys are affected.

Overview of Finerenone in Therapeutics
In the current therapeutic landscape for cardiorenal diseases, finerenone has emerged as a strategic advancement. It has been developed and evaluated across a wide spectrum of clinical studies, including pivotal Phase III clinical trials such as FIDELIO-DKD and FIGARO-DKD, which have assessed its efficacy in patients with chronic kidney disease (CKD) associated with type 2 diabetes mellitus (T2DM). With its favorable receptor selectivity profile and robust evidence for reducing both renal and cardiovascular events, finerenone offers a dual benefit. The drug’s ability to delay the progression of kidney dysfunction while simultaneously reducing the risk of adverse cardiovascular outcomes presents a significant advancement over earlier therapies that were limited by adverse effects such as hyperkalemia. Additionally, current studies suggest that finerenone might also play a role in managing heart failure, expanding its potential therapeutic indications beyond diabetic kidney disease. Thus, finerenone represents an important step forward in the integrated management of patients whose conditions span both renal and cardiac pathologies.

Diseases Treated by Finerenone
Finerenone has been investigated and approved primarily for conditions characterized by chronic kidney damage and associated cardiovascular complications. Its mechanism of action makes it particularly suitable for patients in whom mineralocorticoid receptor overactivation contributes to progressive renal fibrosis and adverse cardiovascular remodeling.

Chronic Kidney Disease
One of the principal diseases for which finerenone is indicated is chronic kidney disease (CKD), especially when it is associated with type 2 diabetes. Diabetes is a leading cause of CKD, and diabetic kidney disease (DKD) represents a major contributor to end-stage kidney disease (ESKD) worldwide. Finerenone has been rigorously evaluated in large-scale, randomized controlled trials to determine its efficacy in slowing kidney disease progression and reducing related complications.

The FIDELIO-DKD trial, for example, focused on adult patients with CKD associated with T2DM, all of whom were receiving optimized renin-angiotensin system (RAS) blockade therapy. In this trial, finerenone significantly reduced the composite primary endpoint comprising kidney failure, a sustained decline of 40% or more in the estimated glomerular filtration rate (eGFR), or renal death. The drug’s renoprotective actions are believed to be due to its capacity to attenuate inflammation and interstitial fibrosis, which are hallmarks of diabetic kidney disease. Similarly, the FIGARO-DKD study extended these findings by evaluating cardiovascular outcomes in a population with milder kidney disease, demonstrating that finerenone could lower the risk of cardiovascular events even in early stages of CKD.

It is important to note that finerenone has been shown to reduce proteinuria, as indicated by significant reductions in the urinary albumin-to-creatinine ratio (UACR), which serves as an early marker of kidney damage. The consistent ability to decrease albuminuria, along with its impact on hard clinical outcomes, underscores its role as a disease-modifying therapy in DKD. Moreover, emerging evidence also suggests that finerenone may benefit patients with CKD not solely driven by diabetes. Although most of the robust data currently available pertain to diabetic kidney disease, ongoing trials are exploring its efficacy in broader CKD populations, including those without diabetes. This expanded focus is particularly relevant given that mineralocorticoid receptor activation is a common underlying factor in CKD irrespective of the primary etiology.

Heart Failure
While the primary label for finerenone has been associated with diabetic kidney disease, its cardioprotective effects have also been prominently highlighted in clinical research. Patients with chronic kidney disease, especially those with diabetes, are at an increased risk of developing cardiovascular complications including heart failure (HF). The overactivation of the MR not only contributes to renal fibrosis but also to cardiac remodeling, leading to conditions such as heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).

Clinical studies have demonstrated that finerenone can reduce the incidence of heart failure hospitalizations. For instance, in the FIDELIO-DKD trial, aside from its renal benefits, finerenone was associated with a statistically significant reduction in the risk of cardiovascular adverse events, predominantly driven by fewer hospitalizations for heart failure. Similarly, the FIGARO-DKD trial demonstrated a reduction in composite cardiovascular outcomes that included cardiovascular death and nonfatal events such as myocardial infarctions and strokes; a considerable proportion of these benefits was attributable to a lower incidence of heart failure events.

Beyond the pivotal DKD trials, additional studies have specifically targeted heart failure. Ongoing clinical trials such as FINEARTS-HF are investigating the clinical efficacy and safety of finerenone in patients with heart failure—particularly in those who are intolerant to conventional steroidal MRAs or have contraindications to their use. These trials are expected to further delineate the role of finerenone in patients with heart failure with mildly reduced or preserved ejection fraction. The observed benefits in heart failure may be related to the drug’s potent anti-inflammatory and anti-fibrotic actions within the myocardium, as well as its ability to modulate serum potassium levels more favorably than traditional agents.

Clinical Efficacy and Safety
The clinical development program for finerenone has generated an extensive body of evidence supporting its efficacy and delineating its safety profile. Both renal and cardiovascular endpoints have been robustly evaluated in multiple large-scale clinical trials, offering a comprehensive understanding of its benefits and risks.

Clinical Trial Results
Finerenone’s efficacy is prominently supported by data from the FIDELIO-DKD and FIGARO-DKD trials. In FIDELIO-DKD, finerenone demonstrated a significant reduction in a composite endpoint that included kidney failure, sustained eGFR decline, and renal death. The trial enrolled thousands of patients with T2DM-associated CKD, and after a median follow-up of approximately 2.6 years, patients on finerenone experienced a reduction in kidney disease progression compared with placebo. Furthermore, the FIGARO-DKD trial, which targeted a cohort with milder kidney impairment but still at risk due to albuminuria, confirmed that finerenone reduced cardiovascular events, particularly hospitalizations for heart failure.

Additional subgroup analyses and pooled data from these studies, sometimes referred to as the FIDELITY analysis, reinforced the dual cardiorenal benefits. This combined analysis confirmed that finerenone reduced composite cardiovascular outcomes by approximately 14% and renal outcomes by nearly 23% compared to placebo. These trials provide evidence that finerenone is capable of both delaying the progression of renal dysfunction and reducing the incidence of cardiovascular events, particularly in high-risk populations such as those with T2DM.

More recent interim data from real-world studies, such as FINE-REAL, have provided additional insights into finerenone’s safety profile in routine clinical practice, confirming that while hyperkalemia remains a concern, its overall incidence is manageable with appropriate monitoring. In the FINE-REAL study, hyperkalemia was observed in approximately 5% of patients, which is lower than the rates typically seen with traditional MRAs and is deemed acceptable in light of the clinical benefits.

Other clinical investigations have also demonstrated significant reductions in UACR, a surrogate marker for kidney damage, after initiation of finerenone therapy. The reduction in albuminuria is both dose-dependent and sustained over time, supporting its therapeutic role in altering the disease trajectory of diabetic kidney disease. Additionally, finerenone’s effect on blood pressure, although modest, does not fully account for its renal and cardiac benefits, further underscoring its role in modulating non-hemodynamic pathways such as inflammation and fibrosis.

Side Effects and Safety Profile
Finerenone exhibits a safety profile that is generally favorable when compared to traditional steroidal MRAs. The most commonly reported adverse event associated with finerenone is hyperkalemia, a well-known class effect related to MR blockade. Despite this, the incidence of hyperkalemia with finerenone has been relatively lower and more manageable. For instance, in the FIGARO-DKD trial, hyperkalemia-related discontinuations occurred in only about 1.2% of patients compared to 0.4% in the placebo group. Routine monitoring of serum potassium levels before and during the course of therapy is recommended in order to mitigate this risk.

Other adverse effects such as hypotension and hyponatremia have been observed but at lower frequencies and are generally transient and manageable with dose adjustments. Importantly, finerenone does not appear to cause the hormonal side effects (e.g., gynecomastia, menstrual irregularities) that are commonly associated with other steroidal MRAs, likely due to its high selectivity for the mineralocorticoid receptor and minimal cross-reactivity with androgen receptors.

Data from multiple clinical studies have also shown that finerenone does not significantly affect glycemic control (HbA1c levels) or body weight, which is an important consideration in patients with T2DM. Moreover, the overall frequency of treatment-emergent adverse events between the finerenone and placebo groups has been similar, with serious adverse events tending to be lower in the finerenone groups, further supporting its safety for long-term use.

Real-world evidence, such as that provided from interim results in observational studies, has complemented the controlled trial data by demonstrating that finerenone’s efficacy and safety profile are reproducible in routine clinical settings. Such data underscore the importance of selecting the correct patient population—especially those already optimized on RAS inhibitor therapy—and ensuring regular monitoring to maintain serum potassium within safe limits.

Future Directions and Research
While finerenone is already well established for the treatment of CKD associated with T2DM and demonstrates promising efficacy in reducing heart failure hospitalizations, numerous avenues for future research and expansion of its clinical application remain under active investigation.

Ongoing Clinical Trials
Several clinical trials continue to expand our understanding of the potential benefits and appropriate patient populations for finerenone. The FINEARTS-HF trial, for example, focuses on the efficacy and safety of finerenone in patients with heart failure who have a reduced or mid-range ejection fraction, particularly those who are either intolerant of or not eligible for treatment with steroidal MRAs. This trial aims to determine whether the cardiorenal benefits of finerenone observed in diabetic kidney disease patients can be extended to a broader heart failure population, including those with heart failure with preserved ejection fraction (HFpEF), a growing and underserved subset of patients.

Additionally, there are studies exploring the use of finerenone in non-diabetic CKD populations, a subject of great interest because mineralocorticoid receptor overactivation is a common pathophysiological mechanism irrespective of the underlying cause of renal dysfunction. One such study, assessing the effectiveness and safety of finerenone in Chinese CKD patients without diabetes, is being conducted as a real-world retrospective study, which could potentially broaden the therapeutic spectrum of the drug.

There are also efforts to investigate combination therapies, evaluating whether the combination of finerenone with other agents that have proven renal or cardioprotective actions—such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists—might offer additive or synergistic benefits. Subgroup analyses, such as those examining the impact of baseline GLP-1 receptor agonist use on finerenone’s efficacy, have suggested that the reduction in albuminuria and the protective effects on kidney and cardiovascular outcomes are maintained regardless of concomitant therapy. These combination strategies are particularly relevant given that guideline-directed therapy for diabetic kidney disease increasingly emphasizes the use of multiple complementary agents.

Emerging Research Areas
Beyond the established indications in diabetic kidney disease and heart failure, emerging research is investigating potential new therapeutic roles for finerenone. Its unique pharmacodynamic properties have sparked interest in evaluating its use in conditions where inflammation and fibrosis play critical roles. For example, preclinical studies have raised the possibility that finerenone could be beneficial in pulmonary arterial hypertension (PAH), where vascular inflammation and remodeling contribute to disease progression. Although such applications are in the early stages of investigation, they open up the possibility of finerenone addressing a broader range of conditions characterized by MR overactivation.

Research is also ongoing to better understand the long-term outcomes associated with finerenone therapy in various patient subgroups. The pharmacokinetic properties of finerenone, such as its short half-life and balanced renal-heart tissue penetration, suggest that dosing regimens could potentially be optimized for different patient profiles. Future studies may focus on tailoring therapy based on factors such as the severity of kidney dysfunction, baseline serum potassium levels, and the presence of comorbid cardiovascular disease, thereby enhancing precision medicine approaches in cardiorenal care.

Another emerging area involves the application of advanced biomarkers to monitor and predict treatment response. There is ongoing work to develop and validate urinary and serum biomarkers that could provide early indications of response to finerenone, allowing clinicians to personalize treatment and adjust dosing before significant clinical deterioration occurs. Moreover, integration of imaging modalities and functional assessments may further refine patient selection and enhance understanding of finerenone’s impact on tissue-level changes in both the heart and kidneys.

Finally, as new regulatory updates and guideline amendments are influenced by recent trial results, it is anticipated that the indications for finerenone could expand further. For instance, updated guidelines from organizations like the American Diabetes Association and Kidney Disease: Improving Global Outcomes (KDIGO) are now considering recent evidence from FIDELIO-DKD and FIGARO-DKD trials, which may pave the way for broader use of finerenone in clinical practice. These future directions highlight the potential for finerenone not only to maintain its current role in diabetic kidney disease management but also to evolve as a versatile treatment option in diverse patient populations.

Conclusion
In summary, finerenone is a highly selective, non-steroidal mineralocorticoid receptor antagonist that offers significant therapeutic benefits for diseases where MR overactivation drives pathological inflammation and fibrosis. It is primarily used in the treatment of chronic kidney disease, especially diabetic kidney disease associated with type 2 diabetes, by significantly reducing the progression of renal dysfunction and lowering outcomes such as kidney failure and cardiovascular events. Moreover, its positive effects on heart failure—demonstrated by reductions in heart failure hospitalizations and improvements in cardiac remodeling—expand its clinical utility, potentially encompassing a broader range of heart failure phenotypes.

On the efficacy and safety front, extensive clinical trial data underscore finerenone’s ability to deliver both renal and cardiovascular protection while maintaining a manageable safety profile. Although hyperkalemia remains the most recognized adverse effect, its incidence is relatively low compared to traditional MRAs, and the absence of hormonal side effects further enhances its appeal. The clinical benefits have been consistently demonstrated in large randomized controlled trials as well as in real-world observational studies, solidifying its role as an important agent in the integrated management of cardiorenal diseases.

Looking forward, ongoing clinical trials in various populations—including non-diabetic CKD patients and heart failure subgroups—and emerging research into potential new indications such as pulmonary arterial hypertension and combination therapy with other novel agents, promise to further expand and refine the therapeutic applications of finerenone. Advanced biomarker studies and personalized dosing strategies are also anticipated to optimize treatment outcomes even further.

Thus, finerenone represents a paradigm shift in addressing the intertwined epidemics of diabetic kidney disease and heart failure. With robust evidence supporting its dual benefits and a favorable safety profile, finerenone not only meets current clinical needs but also has the potential to redefine treatment approaches in a growing array of cardiorenal conditions. The future developments in ongoing trials and emerging research areas are likely to further clarify and extend its indications, ensuring that patients with a wide spectrum of kidney and cardiovascular diseases ultimately benefit from this innovative therapy.