Finerenone: One Fine Option

for CKD in Diabetes?

Morgan Dermody, PharmD, MBA
PGY1 Resident
May 1, 2023
Disclosures:
I have no relevant financial conflicts or other conflicts of interest to
disclose.
Off-label uses of medications will be discussed in this presentation.
Abbreviations Used:
• ACEi: Angiotensin Converting Enzyme Inhibitor
• ACR: Albumin Creatinine Ratio
• ADA: American Diabetes Association
• ARB: Angiotensin Receptor Blocker
• ASCVD: Atherosclerotic Cardiovascular Disease
• DM: Diabetes Mellitus
• DPP-4i: Dipeptidyl Peptidase-4 Inhibitor
• CKD: Chronic Kidney Disease
• eGFR: Estimated Glomerular Filtration Rate
• ESRD: End-stage Renal Disease
• GLP-1 RA: Glucagon-Like Peptide-1 Receptor
Antagonist
• HF: Heart Failure
• HHF: Hospitalization from Heart Failure
• HTN: Hypertension
• KDIGO: Kidney Disease: Improving Global
Outcomes
• MI: Myocardial Infarction
• ns-MRA: Non-Steroidal Mineral Corticoid
Receptor Antagonist
• SCr: Serum Creatinine
• SGLT2i: Sodium-Glucose Cotransporter-2
Inhibitor
• SU: Sulfonylurea
• T2DM: Type 2 Diabetes Mellitus
• TZD: Thiazolidinedione
 Explain the mechanism of action of finerenone

Discuss current guideline

recommendations for management of HF
Learning and CKD in T2DM

Objectives Analyze recent literature published on

finerenone in T2DM

Evaluate finereone’s possible place in therapy

for patients with T2DM
Epidemiology of Type 2 Diabetes

28.7 million 37.3 million

~ 8.5 million
adults with United
undiagnosed
a diagnosis States adults

Centers for Disease Control and Prevention: National Diabetes Statistics Report.
Epidemiology in Type 2 Diabetes:
Chronic Kidney Disease Heart Failure

Diabetes is the leading cause of Those with DM are 2-4 times

CKD and ESRD (US and World) more likely to have HF

Approximately 25-30% of those Risk of HF may be slightly

with diabetes have CKD higher in women than in men
with diabetes

International Diabetes Federation. 2017.

United States Renal Data System. 2017.
Ohkuma T, et al. Diabetologia. 2019;62(9):1550-60.
 HF
64 million
people
HF + CKD HF + DM
42-53% 25-40%
Global 16%

Rates CKD CKD + DM

DM
476 million
698 million 40% people
people

Adapted From: Vijay K, et al. Cardiorenal Med.2022;12:1-10.

Type 2 Diabetes: Pathophysiology

https://www.researchgate.net/figure/The-ominous-octet-pathophysiologic-abnormalities-in-type-2-diabetes-mellitus-7_fig2_46393919

Trujillo J, et al. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12e.

Guideline Recommendations
2023 ADA
Standards
of Care

ElSayed NA, et al. Diabetes Care; 2023;46(Suppl. 1):S140-S157.

2023 ADA Standards of Care
• Identify co-morbid conditions to • Select appropriate therapies based
drive therapy choices: on patient specific factors:
• ASCVD • Biguanide
• Indicators of high risk (age > 55 + 2 • GLP-1 RA
or more additional risk factors • SGLT2i
[obesity, HTN, smoking, • TZD
dyslipidemia, or albuminuria])
• DPP-4i
• Heart Failure
• SU
• Chronic Kidney Disease
• Insulin

ElSayed NA, et al. Diabetes Care; 2023;46(Suppl. 1):S140-S157.

 2023 ADA Standards of Care
Chronic Kidney Disease Heart Failure
SGLT2i with primary evidence of
reducing CKD (preferred) or GLP-1A SGLT2i with proven HF benefit
with proven CVD benefit

Consider incorporating GLP-1A if on Consider other therapies if additional

SGLT2i or vice versa cardiorenal risk reduction or glycemic
lowering is needed

Consider other therapies if additional

cardiorenal risk reduction or glycemic
lowering is needed
ElSayed NA, et al. Diabetes Care; 2023;46(Suppl. 1):S140-S157.
2023 ADA Standards of Care in T2DM and CKD
In those with DM and HTN an ACEi or ARB is recommended for those with
moderately or severely increased UACR and/or an eGFR of < 60 mL/min/1.73m2

In those with DM and CKD, consider use of an SGLT2i, a GLP1-RA, or a ns-MRA

additionally for cardiovascular risk reduction

In those with DM and CKD (eGFR > 20 mL/min/1.73m2) an SGLT2i is

recommended to reduce CKD progression and cardiovascular events

In those with DM and CKD ns-MRA is recommended to reduce CKD progression

and cardiovascular events

ElSayed NA, et al. Diabetes Care; 2023;46(Suppl. 1):S191-S202.

2022 ADA & KDIGO Consensus Report
A ns-MRA with proven kidney and cardiovascular benefit is recommended
in patients with:

Normal
Type 2
eGFR > 25 Serum Albuminuria
Diabetes
mL/min/1.73m2 Potassium (ACR > 30 mg/g)
Mellitus
Level

de Boer IH, et al. Diabetes Care. 2022;45:3075-90.

 Kidney Function Assessment: Calculations
National Kidney Foundation and American Society of
Nephrology Task Force on Reassessing the Inclusion of Race in
Diagnosis Kidney Disease

Final Recommendation: utilize the eGFR 2021 CKD EPI

creatinine equation that estimates kidney function without
using race

Increase utilization of cystatin C combined with creatinine

for a reliable way to assess kidney function

National Kidney Foundation. 2021.

 Non-steroidal Mineral Corticoid
Receptor Antagonist

Finerenone FDA Approved July 09, 2021

Approved for use in CKD associated

with Type 2 Diabetes

Lexi-drugs/Finerenone
Finerenone: Mechanism of Action

https://www.sciencedirect.com/science/article/pii/S1043661821004436

Kolkhof P, et al. Pharmacol Res. 2021;172:1-13.

Finerenone: Initial Dosing

eGFR ≥60 mL/minute/1.73 m2: 20 mg once daily

eGFR ≥25 to <60 mL/minute/1.73 m2: 10 mg once daily

eGFR <25 mL/minute/1.73 m2: Use not recommended

Lexi-drugs/Finerenone
Finerenone: Maintenance Dosing
Current serum Current finerenone dose
potassium (mEq/L) 10 mg once daily 20 mg once daily
Maintenance: < 4.8 Increase to 20 mg Continue 20 mg
based on once daily once daily
serum
potassium > 4.8 to 5.5 Continue 10 mg Continue 20 mg
four weeks once daily once daily
after > 5.5 Interrupt therapy; may Interrupt therapy;
initiation consider restarting restart at 10 mg once
10 mg once daily when daily when serum
serum potassium potassium ≤5 mEq/L
< 5 mEq/L

Lexi-drugs/Finerenone
Knowledge Check
Define the mechanism of finerenone:
A. Inhibition of renin-angiotensin aldosterone system

B. Selective antagonism of mineralocorticoid receptor-mediated sodium

reabsorption and over-activation in epithelial and non-epithelial tissue

C. Competes with aldosterone for receptor sites in the distal renal tubules
to promote sodium excretion

D. Promotion of the excretion of sodium via specific sodium-glucose co-

transporters to reduce overall blood glucose levels
What is the recommended eGFR cutoff for
the initiation of finerenone?
A. eGFR < 25 mL/minute/1.73m2

B. eGFR < 35 mL/minute/1.73m2

C. eGFR < 60 mL/minute/1.73m2

D. eGFR < 90 mL/minute/1.73m2

Literature Review
FIGARO-DKD
FIGARO-DKD: international, randomized, double-blind, placebo-controlled,
phase III, multicenter

1:1 randomization to once daily finerenone (10 or 20 mg) vs. placebo

Pre-specified Outcomes: Time to new-onset HF, composite of time to HF-

related death or first HHF, time to first HHF, composite of time to CV death or
total HHF, and time to total HHF

Filippatos G, et al. Circ. 2022;145:437-47.

FIGARO-DKD Criteria
INCLUSION
• > 18 years of age
• Clinical diagnosis of T2DM and
albuminuric CKD
• Treatment with a maximum
tolerated dose of an ACEi or ARB
• Serum potassium of < 4.8 mEq/L
EXCLUSION
• Symptomatic chronic HF with reduced
ejection fraction (NYHA class II-IV)
• Known significant non-diabetic kidney
disease
• Stroke/Transient ischemic attack
• Acute Coronary Syndrome
• HHF in previous 30 days
• Recent history of dialysis for acute
kidney failure; kidney transplant;
uncontrolled HTN
Filippatos G, et al. Circ. 2022;145:437-447.
FIGARO-DKD Baseline Characteristics
With Heart Failure (n = 571) Without Heart Failure (n = 6781)

• Male Sex: 61.3% • Male Sex: 70.1%

• White: 87.9% • White: 70.4%
• African American: 4.6% • African American: 3.4%
• Age (mean): 65.6 years • Age (mean): 64 years
• Serum Potassium (mean): 4.4 mEq/L • Serum Potassium (mean): 4.3 mEq/L
• eGFR (mean): 63.4 mL/min/1.73m2 • eGFR (mean): 68.2 mL/min/1.73m2
• UACR (mean): 264.4 mg/g • UACR (mean): 313.2 mg/g

Filippatos G, et al. Circ. 2022;145:437-47.

FIGARO-DKD Outcomes
Primary Outcome
• New-onset HF occurred in 1.9%
of finerenone patients compared
to 2.8% of placebo
(HR 0.68; 95% CI, 0.5-0.93;
P = 0.0162)
• Incidences of all HF outcomes
analyzed were significantly lower
with finerenone vs. placebo
HF Outcomes
• 18% lower risk of CV death or
HHF (HR, 0.82; 95% CI, 0.7-0.95;
P = 0.011)
• 29% lower risk of first HHF
(HR, 0.71; 95% CI, 0.56-0.9;
P = 0.0043)
• 30% lower rate of total HHF
(rate ratio 0.7; 95% CI, 0.52-0.94)
Filippatos G, et al. Circ. 2022;145:437-47.
FIGARO-DKD Limitations

Small
HF Definition Subgroup 72% White
Sample Size

Pre-existing
69% Male
HF Regimens

Filippatos G, et al. Circ. 2022;145:437-47.

FIDELIO-DKD

Phase III, randomized, double-blind, placebo-controlled, multi-center

Primary Outcome: Composite of kidney failure, a sustained decrease

of > 40% in eGFR from baseline over a period of > 4 weeks, or death
from renal causes

Secondary Outcome: Composite of death from cardiovascular causes,

nonfatal MI, nonfatal stroke, or hospitalization for heart failure

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.

FIDELIO-DKD Criteria
INCLUSION
• > 18 years of age
• DMT2 and CKD
• Treatment with a maximum
tolerated dose of an ACEi or ARB
• Serum potassium of < 4.8 mEq/L
EXCLUSION
• Symptomatic chronic HF with reduced
ejection fraction (NYHA class II-IV)
• Known significant non-diabetic kidney
disease
• Stroke/Transient ischemic attack
• ACS
• Dialysis within 12 weeks of run-in visit
for acute kidney failure; kidney
transplant; uncontrolled HTN
Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.
FIDELIO-DKD Baseline Characteristics

70.2% Male 63.3% White 4.7% Black

eGFR: 44.3 UACR > 300:

65.6 Years
mL/min/1.73m2 87.5%

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.

FIDELIO-DKD Outcomes
• Primary Outcome: Composite of kidney failure, a sustained decrease of > 40%
in eGFR from baseline over a period of > 4 weeks, or death from renal causes

• Significantly lower in finerenone (17.8%) vs. placebo (21.1%)

(HR 0.82; 95% CI, 0.73-0.93; P = 0.001)

• After 3 years, the number of patients needed to be treated with finerenone

to prevent one primary outcome was 29 (95% CI, 16-166)

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.

FIDELIO-DKD Outcomes
• Secondary Outcome: Composite of death from cardiovascular causes,
nonfatal MI, nonfatal stroke, or hospitalization for heart failure

• Significantly lower in finerenone (13%) vs. placebo (14.8%)

(HR 0.86; 95% CI, 0.75-0.99)

• All components had lower incidence compared to placebo with the

exception of nonfatal stroke (similar incidence)

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.

FIDELIO-DKD Limitations

Exclusion of
Rate of
non-albuminuric
Advanced CKD
CKD

Exclusion of CKD
not due to 4.7% Black
T2DM

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.

 Aim: perform an individual
patient-level pre-specified
pooled efficacy and safety
analysis in CKD patients

FIDELITY Methods: combined FIGARO-

DKD and FIDELIO-DKD for pre-
Analysis specified analysis

Outcomes: included both

cardiovascular and renal
composite outcomes

Agarwal R, et al. Eur Heart J. 2022;43:474-84.

FIDELITY Analysis Criteria
INCLUSION
• > 18 years of age
• DMT2 and CKD
• Treatment with a maximally
tolerated ACEi or ARB
EXCLUSION
• Patients excluded from this
analysis were excluded based on
the trial from which they were
pulled: FIGARO-DKD vs. FIDELIO-
DKD
Agarwal R, et al. Eur Heart J. 2022;43:474-84.
FIDELITY Analysis Baseline Characteristics

4%
69.8% Male 68.1% White Black/African
American

7.7% Heart eGFR: 57.6

64.8 Years
Failure mL/min/1.73m2
FIDELITY Analysis Efficacy Findings
Composite Cardiovascular Outcomes
• Time to CV death, non-fatal MI, non-fatal stroke, HHF occurred in 12.7% of
finerenone patients and 14.4% of placebo
(HR, 0.86; 95% CI, 0.78-0.95; P=0.0018)

Composite Kidney Outcomes

• Time to first onset of kidney failure, sustained > 57% decrease in eGFR from
baseline over > 4 weeks, or renal death were significantly lower in the
finerenone group (5.5%) vs. placebo (7.1%)
(HR, 0.77; 95% CI, 0.67-0.88; P=0.0002)

Agarwal R, et al. Eur Heart J. 2022;43:474-84.

FIDELITY Analysis Safety Findings
Renal-Related Adverse Events
• Similar between groups (includes AKI)

Hyperkalemia-Related Adverse Events

• More frequent with finerenone (14%) vs. placebo (6.9%).
• 0 events were fatal, only a small proportion led to permanent
treatment discontinuation (1.7% finerenone vs. 0.6% placebo) or
hospitalization (0.9% vs. 0.2%)

Agarwal R, et al. Eur Heart J. 2022;43:474-84

FIDELITY Analysis Limitations

70% Male 30% Female 68% White

Exclusion of
4% Black/African Emergence of
those with non-
American SGLT2i’s
albuminuric CKD

Agarwal R, et al. Eur Heart J. 2022;43:474-84.

Cardiovascular Events with Finerenone in
Kidney Disease and Type 2 Diabetes
Phase III, multicenter, randomized, double-blind, placebo controlled

Event-driven with the primary outcome assessed by time-to-event

Primary Outcome: Composite of death from CV causes, non-fatal MI, non-fatal

stroke, or hospitalization for heart failure

Secondary Outcome: Composite of kidney failure, sustained decrease in eGFR

from baseline of > 40%, or death from renal causes

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.

Cardiovascular Events with Finerenone in
Kidney Disease and Type 2 Diabetes Criteria
Inclusion Exclusion
• Urinary albumin creatinine ratio • Urinary albumin creatinine ratio
of 30 to < 300 mg/g and an eGFR of 300-5000 and an eGFR of 25 to
of 25-90 ml/min/1.73m2 < 60 ml/min/1.73m2
OR
• Urinary albumin creatinine ratio
of 300-5000 mg/g and an eGFR of
> 60 ml/min/1.73m2

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.

Cardiovascular Events with Finerenone in Kidney
Disease and Type 2 Diabetes Characteristics

69.4% Male 71.8% White 3.5% Black

eGFR: 67.8
64.1 Years 8.4% SGLT2i
mL/min/1.73m2

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.

Cardiovascular Events with Finerenone in
Kidney Disease and Type 2 Diabetes Outcomes
• Primary Outcome: Composite of death from CV causes, non-fatal MI, non-fatal
stroke, or hospitalization for heart failure

• Significantly lower in the finerenone group (12.4%) vs. placebo (14.2%)

(HR, 0.87; 95% CI, 0.76-0.98; P = 0.03)

• Secondary Outcome: Composite of kidney failure, sustained decrease in eGFR from

baseline of > 40%, or death from renal causes

• No significant difference between groups regarding the first secondary composite

outcome. Analyses of subsequent secondary outcomes are exploratory

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.

 LIMITATIONS:

Cardiovascular
Events with COVID-19 SGLT2i’s
Finerenone in
Kidney Disease
and Type 2
Diabetes 70% Male 72% White

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.

Patient Case
• A 47 YOF presents with PMH of HTN, HLD, T2DM, and CKD. She is on
metformin 2000 mg daily, semaglutide 1 mg weekly, atorvastatin 40 mg
nightly, and losartan 100 mg daily. Today her labs include an eGFR 65
mL/min/1.73m2, SCr 0.7, potassium 4.9 mEq/L, UACR 282 mg/g, and
HgbA1c 7.2%. Vitals include: BP 128/75 mmHg, HR 75 bpm.

• Which of the following would be recommended to help delay progression

of her CKD and reduce her risk of cardiovascular events?
A. Empagliflozin 25 mg daily
B. Finerenone 10 mg daily
C. Finerenone 20 mg daily
D. Lisinopril 10 mg daily
Summary
Guideline Summary: 2023 ADA Standards of
Care in T2DM and CKD

Consider use of an SGLT2i, a

A ns-MRA is recommended
GLP1-RA, or a ns-MRA
to reduce CKD progression
additionally for
and cardiovascular events
cardiovascular risk reduction

ElSayed NA, et al. Diabetes Care; 2023;46(Suppl. 1):S191-S202.

 Guideline Summary

2022 ADA and KDIGO

Consensus Report

Type 2 Diabetes eGFR > 25 Normal Serum Albuminuria

Mellitus mL/min/1.73m2 Potassium Level (ACR > 30 mg/g)

de Boer IH, et al. Diabetes Care. 2022;45:3075-90.

Literature Summary

FIGARO- FIDELO-
Finerenone reduces
DKD Finerenone reduces DKD the risk of CKD
new-onset HF and
progression and CV
improves HF outcomes
events vs. placebo in
in patients with CKD
patients with CKD and
and T2DM vs. placebo
T2DM

Filippatos G, et al. Circ. 2022;145:437-47.

Bakris, GL, et al. N Engl J Med. 2022;383(23):2219-29.
Literature Summary

CV Events
FIDELITY
in CKD
ANALYSIS Finerenone reduces Finerenone improves
risk of CV and renal and DM CV outcomes in
outcomes vs. patients with T2DM
placebo in patients and stage 1-2 CKD
with CKD and T2DM vs. placebo

Agarwal R, et al. Eur Heart J. 2022;43:474-84.

Pitt B, et al. N Engl J Med. 2022;385(24):2252-63.
Conclusions – Personal
Finerenone is safe and effective in reducing CV events in
patients with CKD and T2DM

Finerenone is safe and effective in reducing the risk of renal

events in patients with CKD and T2DM

More evidence is needed to support the use of finerenone to

reduce instance of new onset HF in patients with CKD and T2DM
Finerenone: One Fine Option
for CKD in Diabetes?
Morgan Dermody, PharmD, MBA
PGY1 Resident
May 1, 2023
References
• Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney
disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43:474-484.
• American Diabetes Association (ADA) Professional Practice Committee; Draznin B, Aroda VR, Bakris G, et al. 11th ed. Chronic kidney disease
and risk management: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(suppl 1):S175-S184.
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2022;383(23):2219-2229.
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report/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdiabetes%2Fdata%2Fstatistics%2Fstatistics-report.html (Accessed on
February 24, 2023).
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References Continued
• Filippatos G, Agarwal R, Anker SD, et al. on behalf of the FIGARO-DKD Investigators. Finerenone Reduces Risk of Incident Heart Failure in Pati
ents With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial. Circ. 2022;145:437-447.
• Finerenone. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2021 [updated 01 Feb 2023; cited 15 Feb 2023]. A
vailable from: http://online.lexi.com. Subscription required to view.
• International Diabetes Federation. IDF Diabetes Atlas. International Diabetes Federation, editor, Brussels, Belgium 2017.
• Kolkhof P, Joseph A, Kintscher U. Nonsteroidal mineralcorticoid receptor antagonism for cardiovascular and renal disorders – new perspectiv
es for combination therapy. Pharmacol Res. 2021;172:1-13.
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ney.org/newsletter/changes-to-egfr-calculation-and-what-means-people-living-kidney-disease (Accessed on February 24, 2023).
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-analysis of 47 cohorts including 12 million individuals. Diabetologia. 2019;62(9):1550-1560
• Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med.
2022;385(24):2252-2263.
• Trujillo J, Haines S. Diabetes Mellitus. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Michael Posey LL. eds. DiPiro’s Pharmacotherapy
: A Pathophysiologic Approach, 12e. McGraw Hill; 2023. Accessed February 15, 2023. https://accesspharmacy-mhmedical-com.ezproxy.butle
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Bethesda, MD 2017.
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