Pharmacotherapy considerations with finerenone in the treatment of chronic kidney disease associated with type 2 diabetes

Abstract Purpose This review provides an overview of the management of chronic kidney disease (CKD) associated with type 2 diabetes (T2D), how the novel treatment class of nonsteroidal mineralocorticoid receptor antagonists (MRAs) fits within the treatment landscape, and how pharmacists can contribute to the multidisciplinary care of patients with CKD associated with T2D. Summary Optimizing pharmacotherapy for patients with CKD associated with T2D is critical to prevent or slow progression to end-stage kidney disease and reduce the incidence of cardiovascular events. However, many patients with CKD receive suboptimal treatment, in part because of the high complexity of care required, a lack of disease recognition among providers and patients, and a failure to utilize new kidney-protective therapies. Finerenone is the first nonsteroidal, selective MRA to be approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of adult patients with CKD associated with T2D. Clinical trials have demonstrated that finerenone significantly reduces the risk of cardiorenal disease progression vs placebo and has a reduced risk of hyperkalemia compared to traditional steroidal MRAs. Initiation of finerenone should follow evaluation of baseline estimated glomerular filtration rate and serum potassium levels. Consideration of potential drug-drug interactions, follow-up monitoring of potassium levels, and coordination of changes in pharmacotherapy across the patient care team are also important. Conclusion Finerenone is a valuable addition to the treatment landscape for CKD associated with T2D. Through their expertise in medication management, transitions of care, and patient education, clinical pharmacists are well positioned to ensure patients receive safe and effective treatment.

C hronic kidney disease (CKD) is a major contributor to global morbidity and mortality, with a reported prevalence of 9.1% in 2017. 1 It is classified based on cause, rate of glomerular filtration (assessed by estimated glomerular filtration rate, or eGFR), and albuminuria category (assessed by urinary albumin-to-creatinine ratio, or UACR). 2,3n the US, the prevalence of CKD in the adult population was reported to range from 13% to 15% between 2003 and 2018 based on single examinations of eGFR or albuminuria. 4CKD is associated with large healthcare expenditures, with spending for beneficiaries with CKD accounting for approximately 30% of total Medicare fee-for-service spending in 2019. 4yperglycemia and hypertension are key contributors to the progression of kidney disease, and both are Pharmacotherapy considerations with finerenone in the treatment of chronic kidney disease associated with type 2 diabetes associated with type 2 diabetes (T2D). 5onsequently, the prevalence of CKD among patients with T2D in the US is between 35% and 40%, which is considerably higher than in the general population. 4,6Patients with CKD associated with T2D have high rates of progression to end-stage kidney disease (ESKD) and the accompanying burden of cardiovascular disease (CVD). 7KD management requires a multifactorial approach encompassing lifestyle and pharmacological interventions that necessitate the input and coordination of a multidisciplinary team (MDT). 8This is further complicated by high rates of comorbidities and polypharmacy. 8n addition, kidney disease can result in significant changes in the pharmacokinetic and pharmacodynamic properties of many medications. 9][11] Early identification and initiation of interventions to prevent or slow disease progression are imperative, but many patients receive suboptimal treatment, in part because of a lack of disease recognition among providers and patients, the high complexity of care required, and a failure to utilize new kidney-protective therapies. 12The selective nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone is the latest kidney-protective agent to be approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with CKD associated with T2D. 13 It is indicated to reduce the risk of sustained eGFR decline, ESKD, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure. 14inerenone has the most advanced development program of drugs in its class; however, several other nsMRAs are in development but have not been approved by FDA, including AZD9977, apararenone, KBP-5074, and esaxerenone. 13

Objectives
The aim of this review is to provide an overview of the management of CKD associated with T2D, with a focus on the role of finerenone within a rapidly changing treatment landscape.We will provide guidance on the safe and effective use of finerenone, including pharmacokinetics, dosing, risk assessment for and management of hyperkalemia, and potential drugdrug interactions (DDIs).Finally, we will consider how pharmacists can contribute to the multidisciplinary care of patients with CKD associated with T2D.

Search strategy
PubMed was reviewed for articles published up until January 2023 that included the terms "finerenone," "BAY94-8862," and/or "hyperkalemia."The references cited by pertinent articles were also searched for relevant publications.

Diagnosis and clinical management of CKD associated with T2D
The American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) organization, which issue separate guidelines for the management of CKD, recently released a consensus statement covering broad recommendations for management of CKD associated with T2D and specific guidance on the use of cardiorenal protective agents (summarized in Figure 1). 2,3,15The overall goals of disease management are to preserve organ function and attain intermediate targets for glycemia, blood pressure, and lipids through lifestyle interventions and pharmacological therapies if required. 15Recommended pharmacological therapies are summarized in Table 1.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, metformin, statins, and renin-angiotensin system (RAS) inhibitors are recommended as firstline therapies.Metformin will usually form the basis of glycemic control, but it is contraindicated in patients with severely decreased eGFR (<30 mL/ min/1.73m 2 ). 15SGLT2 inhibitors provide glycemic control as well as cardiorenal protection and may be used independently of metformin.The glucose-lowering effect of SGLT2 inhibitors is blunted at eGFRs of less than 45 mL/min/1.73m², but these agents offer residual cardiorenal protection as eGFR declines to 25 mL/min/1.73m². 2 Statins are recommended for all patients with CKD associated with T2D for prevention or management of atherosclerotic CVD, and RAS inhibition with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) is recommended for patients with hypertension and albuminuria. 15Despite being the standard of care for CKD associated with T2D for almost 20 years, ACE inhibitors and ARBs are widely underutilized, potentially because of concerns over complications such as acute kidney injury and hyperkalemia. 12A US registry study KeY POinTS of data gathered from 2007 to 2017 reported that only 20.5% of all patients with CKD (N = 606,064) were prescribed an ACE inhibitor or ARB, and usage among patients with CKD and hypertension was only 25.9%. 16This highlights the challenges that exist in ensuring that patients with CKD receive optimal treatment.Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended if additional risk factors are present.GLP-1RAs should be considered for patients who do not reach glycemic targets with metformin, which reflects the fact that most patients in clinical trials of GLP-1RAs have been on background metformin. 15,17GLP-1RAs also provide protection from CVD events.Positive outcomes for exploratory renal endpoints have been reported in several clinical trials, including reduced incidence of albuminuria and slowed eGFR decline, but the renal benefits of GLP-1RAs have not yet been definitively established within a clinical trial. 17Further insight will be provided by the ongoing phase 3 FLOW trial (primary completion date in August 2024), which will assess the impact of the GLP-1RA semaglutide on renal outcomes as a primary endpoint in patients with CKD associated with T2D. 2 Steroidal MRAs, such as firstgeneration spironolactone and second-generation eplerenone, are indicated for the management of hypertension as well as heart failure with reduced ejection fraction, primary hyperaldosteronism (spironolactone only), and edema in cirrhosis (spironolactone only). 18,19They are not recommended in patients with severe kidney disease or ESKD, and eplerenone is contraindicated in patients with T2D Figure 1.Graphical article summary.Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (nsMRA) approved by the US Food and Drug Administration and European Medicines Agency to treat adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).ACR indicates albumin-to-creatinine ratio; ADA, American Diabetes Association; CVD, cardiovascular disease; ESKD, end-stage kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes; RASi, renin-angiotensin system inhibitor; SGLT2i, sodium-glucose cotransporter-2 inhibitor.and microalbuminuria because of an increased risk of hyperkalemia. 15,18,19he ADA and KDIGO consensus guidelines recommend steroidal MRAs for patients with an eGFR of at least 45 mL/ min/1.73m 2 who have resistant hypertension despite previous treatment with a RAS inhibitor at the maximum tolerated dose as well as the calcium channel blocker dihydropyridine and/ or a diuretic. 15The primary reason for the limited therapeutic role of steroidal MRAs is a risk of hyperkalemia, which is highest in patients with the most severely reduced filtration rates.Although there is some evidence that steroidal MRAs can improve renal outcomes for patients with kidney disease, data are very limited.To date, there have been no large-scale trials investigating renal outcomes in patients with diabetes treated with steroidal MRAs.
nsMRAs were developed to be highly selective for the MR, with the aim of providing cardiorenal protection with a tolerable adverse effect profile. 20Reflecting a reduced risk of hyperkalemia and definitive evidence for long-term cardiorenal protection in patients with CKD associated with T2D, finerenone is recommended for a less restricted subset of patients than the steroidal MRAs. 15inerenone should be considered for patients with an eGFR of at least 25 mL/min/1.73m 2 , normal serum potassium levels (≤5.0 mEq/L), and albuminuria (UACR of ≥30 mg/g). 15 further criterion for finerenone use is that patients are being treated with a maximum tolerated RAS inhibitor dose, which reflects the fact that the cardiorenal protection offered by finerenone in CKD associated with T2D has been demonstrated primarily in patients on a maximum tolerated dose of an ACE inhibitor or ARB.15,21,22

Finerenone mechanism of action and preclinical data
Finerenone is a potent nsMRA with greater selectivity for the MR than the steroidal MRAs spironolactone and eplerenone. 20It has 500-fold-greater selectivity for the MR vs other steroid hormone receptors; by comparison, spironolactone and eplerenone had 3-fold-and 22-fold-greater selectivity, respectively, for the MR vs other steroid hormone receptors in the same assay. 20reclinical studies have demonstrated that finerenone has a unique mechanism of action compared to spironolactone and eplerenone owing to its bulky structure. 20It completely inhibits MR coactivator binding in the presence of aldosterone, as well as in its absence, where it acts as an inverse agonist (Figure 2).In contrast, eplerenone partially inhibits aldosterone-mediated MR coactivator binding and induces coactivator binding in the absence of aldosterone. 23][25] MRAs have the potential to increase potassium levels through inhibition of aldosterone-activated renal sodium reabsorption and potassium excretion. 26The risk of hyperkalemia associated with finerenone appears to be less than that with spironolactone and eplerenone, and this difference may relate to the tissue distribution of these agents.Animal studies have indicated that spironolactone and eplerenone may accumulate more in the kidneys than in the heart, whereas finerenone exhibits balanced accumulation in the heart and kidneys. 27

Clinical trials of finerenone in CvD and kidney disease
][30] The phase 2a ARTS study established safe dosing of finerenone.Assessment of exploratory endpoints suggested that finerenone offered equivalent or greater reductions in albuminuria and N-terminal pro-B-type natriuretic peptide levels than spironolactone, as well as a lower incidence of hyperkalemia. 28The cardiorenal effects of finerenone are not mediated through antihypertensive effects, as evidenced by minimal effects on blood pressure compared to spironolactone and no evidence of a correlation between the antialbuminuric effects of finerenone and blood pressure changes. 28he phase 2b ARTS-HF trial in patients with worsening heart failure who also had T2D and/or CKD demonstrated similar effects of finerenone and eplerenone on N-terminal pro-B-type natriuretic peptide levels and similar safety profiles.The mean change in blood pressure was similar with finerenone and eplerenone. 29The phase 2b ARTS-DN trial demonstrated a dose-dependent reduction in UACR with finerenone in patients with CKD associated with T2D who were being treated with an ACE inhibitor or ARB. 30inerenone was next compared to the standard of care in patients with CKD associated with T2D stabilized on the maximum tolerated dose of an ACE inhibitor or ARB in the phase 3, randomized, double-blind, placebocontrolled FIDELIO-DKD and FIGARO-DKD trials. 21,22The trials had reciprocal primary and secondary endpoints, and the patient populations in each study reflected the focus on renal (FIDELIO-DKD) or CVD (FIGARO-DKD) outcomes. 26The FIDELIO-DKD trial had a primary composite endpoint of renal outcomes and a secondary composite endpoint of CVD outcomes, both of which were met. 22In the FIGARO-DKD trial, CVD outcomes made up the primary composite endpoint and the secondary composite endpoint comprised renal outcomes. 21n the FIGARO-DKD trial, the primary composite endpoint was met but not the secondary composite endpoint. 21In a prespecified patientlevel pooled analysis (FIDELITY) of the outcomes from the FIDELIO-DKD and FIGARO-DKD trials, the incidence of both kidney failure and CVD events was significantly reduced with finerenone compared to placebo, although the CVD benefit was predominantly derived from a reduced incidence of hospitalizations for heart failure. 31cross the FIDELIO-DKD and FIGARO-DKD trials, adverse events (AEs) related to treatment occurred in 18.5% of patients treated with finerenone vs 13.3% of those treated with placebo, and AEs leading to treatment discontinuation occurred in 6.4% vs 5.4% of patients, respectively. 31nvestigator-reported hyperkalemia was more frequent with finerenone (14%) than with placebo (6.9%); incidence of permanent treatment discontinuation due to hyperkalemia was low across study arms but occurred more frequently with finerenone (1.7%) than with placebo (0.6%).No hyperkalemiarelated AEs were fatal. 31

Place in therapy
Cardiorenal protection with finerenone is supported by both the ADA and KDIGO guidelines in patients with CKD and T2D. 2,3,15Appropriate patient selection is crucial, with special attention to ensuring that first-line therapies of metformin, SGLT2 inhibitors, maximum tolerated doses of RAS inhibitors (for hypertensive patients), and moderate-or high-intensity statins have been trialed.Finerenone should  NT-pro-BNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; T2D, type 2 diabetes; UACR, urinary albumin-to-creatinine ratio.
a Secondary endpoints in the phase 2 trials were exploratory; no adjustments were made for multiple comparisons.
Finerenone may also be considered as an add-on therapy to a RAS inhibitor for patients who do not tolerate or are ineligible for an SGLT2 inhibitor. 3ture outlook

Continued from previous page
It will be important to define where finerenone best fits within the treatment landscape for CKD associated with T2D, particularly in relation to SGLT2 inhibitors and GLP-1RAs.Further research is needed to determine the relative effects of these agents and classes in different patient populations and whether they should be used in combination.This is an interesting concept because these agents have different mechanisms of action and may, therefore, have the potential to provide additive or synergistic treatment effects.SGLT2 inhibitors provide cardiorenal protection and help to improve glycemic control, but their glucose-lowering effects are blunted in patients with an eGFR of below 45 mL/ min/1.73m². 2 For these patients, additional studies are needed to determine whether cardiorenal protection is best provided by an SGLT2 inhibitor, finerenone, or use of both therapies.An exploratory analysis of patients receiving an SGLT2 inhibitor at baseline who were treated with finerenone (n = 124) in the FIDELIO-DKD trial reported numerically lower rates of hyperkalemia-related AEs and greater reductions in UACR compared to those not receiving an SGLT2 inhibitor at baseline (n = 2,703). 32urther clarity is anticipated from the prospective phase 2 CONFIDENCE study. 33In this ongoing study, approximately 807 patients with CKD associated with T2D (eGFR of 30-90 mL/ min/1.73m 2 ) were randomized to receive monotherapy with finerenone, monotherapy with the SGLT2 inhibitor empagliflozin, or combination therapy with finerenone and empagliflozin.With an estimated primary completion date in November 2023, the CONFIDENCE study aims to determine whether dual therapy with finerenone and an SGLT2 inhibitor is superior to treatment with either agent alone.Additionally, analysis of the outcomes for patients in the 2 monotherapy arms may provide some answers as to the relative cardiorenal protection provided by finerenone vs empagliflozin at lower levels of kidney function. 34ith regard to GLP-1RAs, a post hoc exploratory analysis of the FIDELIO-DKD trial found no evidence for an increased benefit of baseline GLP-1RA use in patients who were treated with finerenone (n = 189) compared to patients treated with finerenone without baseline GLP-1RA use (n = 2,638). 35t the time of writing, no prospective clinical trials were being planned to evaluate the combination of finerenone and GLP-1RAs in patients with CKD associated with T2D.

Pharmacotherapy considerations for finerenone
Pharmacokinetics.Finerenone is administered orally and is rapidly absorbed, with the maximum serum concentration (C max ) reached between 0.5 and 1.25 hours after dosing. 14Absolute bioavailability is approximately 44%, predominantly because of first-pass metabolism by cytochrome P450 family 3 subfamily A member 4 (CYP3A4) in the gut wall and liver. 14,36Food does not have a clinically significant impact on finerenone bioavailability, although high-fat and high-calorie foods affect the rate of absorption. 14,37inerenone is metabolized to inactive metabolites by CYP3A4 (~90%) and CYP2C8, and approximately 80% of the administered dose is eliminated in urine, with the remainder eliminated in feces. 14The terminal half-life is between 2 and 3 hours, and systemic blood clearance is 25 L/h. 14ild renal impairment has no clear effect on finerenone bioavailability or C max .Moderate hepatic impairment, however, results in a 38% increase in finerenone area under the plasma concentration-time curve (AUC) and a 55% increase in the AUC of unbound finerenone compared to healthy individuals, with no change in C max . 38osing considerations.Finerenone is available in 10-and 20-mg film-coated tablets, with a target dose of 20 mg once daily. 14The recommended starting dose is dependent on eGFR and is 20 mg once daily for patients with normal or mildly reduced eGFR (≥60 mL/min/1.73m²), which is reduced to 10 mg once daily for those with more severe renal impairment (25 to 59 mL/min/1.73m²); initiation is avoided in patients with an eGFR of below 25 mL/min/1.73m² (Figure 3). 14he tablets, which are not scored, may be crushed and administered orally with water or soft foods for patients unable to swallow them whole. 14 missed dose should be taken as soon as possible but only on the day it was missed. 14yperkalemia: risk assessment and management.Serum potassium levels should be evaluated before initiation of finerenone (Figure 3).Treatment should not be initiated if the serum potassium concentration is above 5.0 mEq/L, but initiation may be considered if the concentration is greater than 4.8 but not above 5.0 mEq/L based on clinical judgment, with close monitoring of potassium levels within the first 4 weeks. 14For patients with a baseline serum potassium level of 4.8 mEq/L or less, repeat potassium measurement should be performed within 4 weeks of finerenone initiation and the finerenone dose should be adjusted if the serum potassium concentration is more than 4.8 mEq/L but less than or equal to 5.5 mEq/L.Finerenone should be withheld if the serum potassium concentration is more than 5.5 mEq/L and restarted at 10 mg once daily only when levels are 5.0 mEq/L or less. 14loser monitoring is recommended for patients with high baseline potassium levels and a low eGFR, as well as other risk factors such as the presence of CVD and the potential for DDIs. 39atients with CKD associated with T2D are likely to be on other medications associated with a risk of hyperkalemia at initiation of finerenone, such as an ACE inhibitor or ARB. 2,3Use of medications associated with a risk of hypokalemia, such as loop and thiazide diuretics, must also be considered because dose adjustments or cessation of these medications may result in fluctuations in serum potassium levels. 40Additional risk factors such as male sex, race, and diet are unlikely to affect the management of hyperkalemia in isolation but may have additive effects. 39n clinical practice, it is important to be aware of the potential for variability arising from methodological factors, particularly for patients in the window where clinical judgment may be exercised (with a serum potassium concentration of >4.8 to 5.0 mEq/L). 14,39oor phlebotomy technique may cause pseudohyperkalemia due to hemolysis; excessive patient fist clenching during blood draws can have the same outcome through hypoxia-induced elevation of serum potassium levels.Potassium levels also fluctuate with circadian rhythm by about 0.60 mEq/L throughout the day, so the timing of blood draws may need to be considered with borderline results. 41anagement of hyperkalemia differs between chronic and acute cases. 39he objective in management of acute hyperkalemia is to prevent or reduce the risk of cardiac arrhythmia, whereas treatment of chronic hyperkalemia, which is likely to be detected in routine monitoring and is often asymptomatic, is aimed at normalizing or reducing potassium levels to prevent acute hyperkalemia. 39atients with chronic hyperkalemia should be advised to moderate dietary potassium intake and to avoid other sources of potassium, such as supplements and salt substitutes 3,39 Working with a renal dietitian as part of the MDT may be helpful.Medications should be reviewed with dose optimization considered for RAS inhibitors. 3,39The risks associated with hyperkalemia should be weighed against the risk of downtitration or withdrawal of RAS inhibitors. 42In the case of ACE inhibitors and ARBs, it is important to consider that a majority of patients in the pivotal trials (70% in FIDELIO-DKD and 69% in FIGARO-DKD) were receiving an ACE inhibitor or ARB dose above the minimum label-recommended dose at baseline. 21,22Therefore, withdrawing or interrupting treatment with finerenone may be favored over adjustment of the ACE inhibitor or ARB dose to the minimum label-recommended dose in a situation where hyperkalemia requires management.
Use of diuretics and sodium bicarbonate may also be considered. 3,39otassium binders may be used as well, particularly during optimization of the RAS inhibitor dose. 3,39Newer potassium binders such as patiromer and sodium zirconium cyclosilicate are associated with a reduced risk of gastrointestinal symptoms compared to sodium polystyrene sulfonate and calcium polystyrene sulfonate. 43Dis and drug-food interactions with finerenone.The risk of DDIs is primarily influenced by agents that alter metabolism of finerenone, inhibit the RAS system, or increase serum potassium levels (Table 3).The main implication of DDIs and drug-food interactions associated with finerenone is an increased risk of hyperkalemia. 14inerenone is primarily metabolized by CYP3A4, and concomitant use

FINERENONE TO TREAT KIDNEY DISEASE DIABETES
of strong CYP3A inhibitors is contraindicated because of the resultant increase in finerenone exposure. 14oncomitant use of the strong CYP3A inhibitor itraconazole increased the AUC of finerenone by more than 400%. 14Conversely, strong or moderate CYP3A inducers decrease finerenone exposure and may reduce the efficacy of finerenone. 14No clinically significant differences in finerenone pharmacokinetics have been measured with CYP2C8 inhibitors. 14

Special populations
No differences in safety or efficacy have been observed in geriatric populations compared to other adult populations. 14Safety and efficacy of finerenone have not been established in pediatric patients. 14se of finerenone should be avoided in patients with severe hepatic impairment (Child-Pugh class C) but may be used without dose adjustment in patients with mild or moderate impairment (Child-Pugh class A or B).
Additional serum potassium monitoring should be considered in patients with moderate impairment (Child-Pugh class B). 14 There are no data on fetal or maternal outcomes with finerenone use during pregnancy.Animal studies have shown developmental toxicity at exposure levels 4 times those expected in humans. 14Similarly, there are no safety data for human breastfeeding, although animal studies have suggested that finerenone is likely to be present in milk.Consequently, it is recommended avoid breastfeeding during treatment and for 1 day after treatment. 14][11] Communication among established members of the MDT within the areas of primary care, endocrinology, nephrology, and cardiology is important for optimal patient care.
Pharmacists are key to medication selection, optimization, and monitoring, in addition to patient education and counseling, and are essential in helping patients to overcome access and cost barriers.There may also be a daunting list of recommendations associated with prescribed medications, and pharmacists can help to ensure patients understand any mitigation measures and are reassured of the efficacy and safety of their medications.It is especially important that patients be counseled to report any concerns when they arise.
Suboptimal medication adherence is one of the largest problems in healthcare and is highly relevant in CKD associated with T2D, where many patients have a high medication burden and comorbidities. 11Nonadherence results from intentional factors, such as patient beliefs and priorities, and nonintentional factors, such as lack of education, poor organization, and forgetfulness.][11] Finally, pharmacists may be involved with cost-benefit assessment for medications.Early modeling of the use of finerenone treatment in addition to standard of care in CKD associated with T2D predicted a significant cost benefit derived primarily through a reduced risk of ESKD and renal death in advanced CKD. 46 Recently, the FINE-CKD model has been developed, which can be used to produce reliable assessments of the benefits and costs of the use of finerenone in patients with CKD associated with T2D. 47t is important to note that finerenone and the steroidal MRAs have clearly defined and exclusive roles within the ADA and KDIGO guidelines. 2,3,15Steroidal MRAs are recommended as antihypertensives for a more restricted subset of patients than finerenone, which is recommended for cardiorenal protection. 15Additionally, steroidal MRAs are not recommended in patients with severe kidney disease or ESKD, and eplerenone is contraindicated in patients with T2D and microalbuminuria. 18,19Therefore, steroidal MRAs should not be considered substitutes for finerenone in cases where there are cost or access issues.

Conclusion
Finerenone provides cardiorenal protection for patients with CKD associated with T2D through effects on inflammatory and fibrotic pathways distinct from those of other currently approved treatments.An increased risk of hyperkalemia is a limitation of traditional steroidal MRAs, but preclinical and clinical data suggest that this risk is reduced with the nsMRA finerenone and is manageable for most patients.Clinical pharmacists have an opportunity to take a central role in ensuring prescribing practices deliver the benefits of the most effective available treatments to patients living with CKD associated with T2D.
Patient with CKD associated with T2D with an increased risk for CVD and/or CKD progression and/or unable to use an SGLT2i 10 mg daily, with a target of 20 mg daily.Monitor serum potassium within 4 weeks of initiation.Evaluate renal function (eGFR) and serum potassium levels prior to initiating finerenone

Table 1 .
ADA and KDIGO Consensus Recommendations for Pharmacological Management of CKD Associated with T2D 15An additional risk-based therapy for patients who do not meet their individualized glycemic target with metformin and/or an SGLT2i or who are unable to use these drugs AntihypertensiveFirst-line therapy for patients who have hypertension and albuminuria, titrated to the maximum antihypertensive or highest tolerated dose nsMRA (finerenone a ) Cardiorenal protection An additional risk-based therapy for patients with an eGFR of ≥25 mL/min/1.73m 2 , normal serum potassium concentration, and albuminuria (UACR of ≥30 mg/g) despite a maximum tolerated dose of a RAS inhibitor Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; GLP-1RA, glucagon-like peptide-1 receptor agonist; nsMRA, nonsteroidal mineralocorticoid receptor antagonist; RAS, renin-angiotensin system; SGLT2i, sodium-glucose cotransporter-2 inhibitor; T2D, type 2 diabetes; UACR, urinary albumin-to-creatinine ratio.a Finerenone is the only nsMRA approved by the US Food and Drug Administration or European Medicines Agency for the treatment of CKD associated with T2D.

Table 2 .
Clinical Trial Outcomes of Finerenone in Patients With Cardiorenal Disease aM J HealTH-SYST PHaRM | VOLUME 80 | NUMBER 23 | DECEMBER 1, 2023

Table 2 .
Clinical Trial Outcomes of Finerenone in Patients With Cardiorenal Disease aM J HealTH-SYST PHaRM | VOLUME 80 | NUMBER 23 | DECEMBER 1, 2023