Diabetes Mellitus, Noninsulin-Dependent, Type 4

New guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) and a consensus report jointly issued from KDIGO and the American Diabetes Association (ADA) include KERENDIA as part of a comprehensive treatment strategy for patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) who have an estimated glomerular filtration rate of >25 mL/min/1.73 m2, normal serum potassium concentration and albuminuria (urine albumin-to-creatinine ratio >30 mg/g) despite taking a maximum tolerated dose of renin-angiotensin system inhibitor1-3 KERENDIA’s inclusion is supported by data from comprehensive Phase III clinical trial program (FIGARO-DKD and FIDELIO-DKD) investigating kidney and cardiovascular outcomes in more than 13,000 patients with CKD associated with T2D1-4 KERENDIA’s inclusion in new consensus report and updated KDIGO guideline follows additional support in ADA’s Standards of Medical Care in Diabetes—2022 and the American Association of Clinical Endocrinology’s (AACE) Developing a Diabetes Mellitus Comprehensive Care Plan guideline5,6 WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer’s KERENDIA® (finerenone), a first-in-class, non-steroidal mineralocorticoid receptor antagonist (ns-MRA), was recommended as part of a comprehensive treatment strategy for patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) in a newly published update to the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease and in a consensus report jointly issued by KDIGO and the American Diabetes Association (ADA).1-3 KDIGO and the ADA in their combined statement as well as KDIGO in its new clinical guidelines recommended KERENDIA’s inclusion in the treatment plans of patients with CKD associated with T2D who have an estimated glomerular filtration rate (eGFR) of ≥25 mL/min/1.73 m2, normal serum potassium concentration and albuminuria (urine albumin-to-creatinine ratio [ACR] ≥30 mg/g) despite taking a maximum tolerated dose of a renin-angiotensin system (RAS) inhibitor.1-3 KERENDIA was approved by the FDA in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, non-fatal myocardial infarction (MI) and hospitalization for heart failure in adult patients with CKD associated with T2D, based on the results of the FIDELIO-DKD pivotal trial.4 In September 2022, the FDA approved an updated label for KERENDIA to include findings from the Phase III FIGARO-DKD CV outcomes study.4 The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.4 For more information, see “Important Safety Information” below. Recommendations in both clinical guidance documents were based on evidence from the Phase III FIDELIO-DKD and FIGARO-DKD studies as well as results from FIDELITY, the prespecified, exploratory, pooled analysis of both trials, which comprise one of the largest cardiorenal outcomes programs to investigate the occurrence of fatal and non-fatal CV events and progression of kidney disease in patients with CKD associated with T2D in more than 13,000 patients. The program investigated the impact of finerenone in adults with CKD associated with T2D across a range of disease severity (CKD stages 1-4).1-3,7 “KERENDIA’s inclusion in the KDIGO guideline update and ADA and KDIGO consensus report reinforces its foundational and critical role in a multi-pillar treatment strategy for patients with chronic kidney disease associated with type 2 diabetes who seek cardiorenal risk reduction and continue to struggle with persistent albuminuria despite current standard of care treatment,”1-3 said report coauthor George Bakris, Director of the Comprehensive Hypertension Center at the University of Chicago, Illinois. “It is compelling that we now have a general agreement between diabetologists and nephrologists on the use of KERENDIA as part of a treatment plan for patients with chronic kidney disease associated with type 2 diabetes.”8 Over the past year, KERENDIA has been included in clinical recommendations from both the ADA and the American Association of Clinical Endocrinology.5,6 “There has been a longstanding need in the chronic kidney disease space for treatment options and multimodal approaches to patient care,” said Daniel J. Wilson, M.D., FACP, FCCP, Senior Medical Director, Cardiovascular and Renal, U.S. Medical Affairs at Bayer. “Bayer is committed to delivering more treatment options to help patients with chronic kidney disease associated with type 2 diabetes make informed decisions about their health. KERENDIA’s comprehensive clinical trial program, inclusive of patients comprising a range of disease severity and demonstrated evidence in providing cardiorenal risk reduction, has helped establish its place as an important piece of a comprehensive treatment paradigm for chronic kidney disease associated with type 2 diabetes.”1-3 About KDIGO Guideline Update The recently published Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease provides evidence-based recommendations for the management of chronic kidney disease associated with diabetes.1 About ADA and KDIGO’s Consensus Report A joint group of ADA and KDIGO representatives reviewed and developed a series of consensus statements to guide clinical care. With a healthy lifestyle at the core of all treatment, the report aligns clinical recommendations on CKD screening and diagnosis, glycemia monitoring, lifestyle therapies, treatment goals, and pharmacologic management.2,3 About KERENDIA (finerenone) INDICATION: KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).4 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Concomitant use with strong CYP3A4 inhibitors4 Patients with adrenal insufficiency4 WARNINGS AND PRECAUTIONS: Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L.4 Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium.4 MOST COMMON ADVERSE REACTIONS: From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3.9%), and hyponatremia (1.3% vs 0.7%).4 DRUG INTERACTIONS: Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice.4 Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate.4 Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers.4 USE IN SPECIFIC POPULATIONS: Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment.4 Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B).4 Please read the Prescribing Information for KERENDIA. About Finerenone Phase III Clinical Trials Program Having randomized more than 13,000 patients with CKD associated with T2D around the world, the Phase III program with finerenone in CKD associated with T2D comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and CV outcomes.4 FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) studies were randomized, double-blind, placebo-controlled, multicenter studies in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).4 In FIDELIO-DKD, patients needed to either have an UACR of 30 to < 300 mg/g, eGFR 25 to < 60 mL/min/1.73 m2 and diabetic retinopathy, or an UACR of ≥ 300 mg/g and an eGFR of 25 to < 75 mL/min/1.73 m2 to qualify for enrollment.4 In FIGARO-DKD, patients needed to have an UACR of 30 mg/g to < 300 mg/g and an eGFR of 25 to 90 mL/min/1.73 m2, or an UACR ≥ 300 mg/g and an eGFR ≥ 60 mL/min/1.73 m2.4 Both trials excluded patients with known significant non-diabetic kidney disease.4 All patients were to have a serum potassium ≤ 4.8 mEq/L at screening and be receiving standard of care background therapy, including a maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).4 Patients with a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (New York Heart Association class II to IV) were excluded.4 The starting dose of KERENDIA was based on screening eGFR (10 mg once daily in patients with an eGFR of 25 to < 60 mL/min/1.73 m2 and 20 mg once daily in patients with an eGFR ≥ 60 mL/min/1.73 m2).4 The dose of KERENDIA could be titrated during the study, with a target dose of 20 mg daily.4 The primary objective of the FIDELIO-DKD study was to determine whether KERENDIA reduced the incidence of a sustained decline in eGFR of ≥ 40%, kidney failure (defined as chronic dialysis, kidney transplantation, or a sustained decrease in eGFR to < 15 mL/min/1.73 m2), or renal death.4 The secondary outcome was a composite of time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure.4 The primary objective of the FIGARO-DKD study was to determine whether KERENDIA reduced the time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure.4 The secondary outcome was a composite of time to kidney failure, a sustained decline in eGFR of 40% or more compared to baseline over at least 4 weeks, or renal death.4 In FIDELIO-DKD, a total of 5674 patients were randomized to receive KERENDIA (N=2833) or placebo (N=2841) and were followed for a median of 2.6 years.4 The mean age of the study population was 66 years, and 70% of patients were male.4 This global trial population was 63% White, 25% Asian, and 5% Black (24% Black in the US).4 At baseline, the mean eGFR was 44 mL/min/1.73 m2, with 55% of patients having an eGFR < 45 mL/min/1.73 m2.4 Median urine albumin-to-creatinine ratio (UACR) was 852 mg/g, mean glycated hemoglobin A1c (HbA1c) was 7.7%, and the mean blood pressure was 138/76 mmHg.4 Approximately 46% of patients had a history of atherosclerotic cardiovascular disease and 8% had a history of heart failure.4 At baseline, 99.8% of patients were treated with an ACEi or ARB.4 Approximately 97% were on an antidiabetic agent (insulin [64.1%], biguanides [44%], glucagon-like peptide-1 [GLP-1] receptor agonists [7%], sodium-glucose cotransporter 2 [SGLT2] inhibitors [5%]), 74% were on a statin, and 57% were on an antiplatelet agent.4 In FIGARO-DKD, a total of 7352 patients were randomized to receive KERENDIA (N=3686) or placebo (N=3666) and were followed for 3.4 years.4 As compared to FIDELIO-DKD, baseline eGFR was higher in FIGARO-DKD (mean eGFR 68, with 62% of patients having an eGFR ≥ 60 mL/min/1.73 m2) and median UACR was lower (308 mg/g).4 Otherwise, baseline patient characteristics and background therapies were similar in the two trials.4 In FIDELIO-DKD, KERENDIA reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥ 40%, kidney failure, or renal death (HR 0.82, 95% CI 0.73-0.93, P=0.001).4 The treatment effect reflected a reduction in a sustained decline in eGFR of ≥ 40% and progression to kidney failure.4 There were few renal deaths during the trial.4 KERENDIA also reduced the incidence of the secondary composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non-fatal stroke or hospitalization for heart failure (HR 0.86, 95% CI 0.75-0.99, P=0.034).4 The treatment effect reflected a reduction in CV death, non-fatal MI, and hospitalization for heart failure.4 The treatment effect on the primary and secondary composite endpoints was generally consistent across subgroups.4 In FIGARO-DKD, KERENDIA reduced the incidence of the primary composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (HR 0.87, 95% CI 0.76-0.98, P=0.026).4 The treatment effect was mainly driven by an effect on hospitalization for heart failure, though CV death also contributed to the treatment effect.4 The treatment effect on the primary composite endpoint was generally consistent across subgroups, including patients with and without pre-existing cardiovascular disease.4 The secondary composite outcome of kidney failure, sustained eGFR decline of 40% or more or renal death occurred in 350 patients (9.5%) in the finerenone group and in 395 (10.8%) in the placebo group (HR=0.87, 95% CI 0.76-1.01).4,9 The safety of KERENDIA was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter pivotal phase 3 studies, FIDELIO-DKD and FIGARO-DKD, in which a total of 6510 patients were treated with 10 or 20 mg once daily over a mean duration of 2.2 and 2.9 years, respectively.4 Overall, serious adverse events occurred in 32% of patients receiving KERENDIA and in 34% of patients receiving placebo in the FIDELIO-DKD study; the findings were similar in the FIGARO-DKD study.4 Permanent discontinuations due to adverse events also occurred in a similar proportion of patients in the two studies (6-7% of patients receiving KERENDIA and in 5-6% of patients receiving placebo).4 From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3.9%), and hyponatremia (1.3% vs 0.7%).4 The most frequently reported (≥ 10%) adverse reaction in both studies was hyperkalemia.4 Hospitalization due to hyperkalemia for the KERENDIA group was 0.9% vs 0.2% in the placebo group across both studies.4 Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving KERENDIA versus 0.6% of patients receiving placebo across both studies.4 About Chronic Kidney Disease Associated With Type 2 Diabetes Patients with CKD associated with T2D are three times more likely to die from a CV-related cause than those with T2D alone.10 CKD is a serious and progressive condition that is generally underrecognized.11 CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.12-14 Approximately 40% of all patients with T2D develop CKD.14 Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.12,13,15,16 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.17-19 About Bayer’s Commitment in Cardiovascular and Kidney Diseases A leader in the CV space, Bayer upholds a long-standing commitment to delivering science for a better life by advancing innovative treatments. Bayer’s cardiorenal franchise, which began with the discovery and development of a number of vital therapies, now includes a number of products and compounds in various stages of preclinical and clinical development with the potential to impact the way that CV and kidney diseases are treated. Bayer is focused on advancing new treatment approaches for areas of high unmet medical need in CV and kidney diseases by identifying resources and programs aimed at better understanding the real-world management of CKD, expanding screening and early care management for CKD, aligning with and supporting groups and institutions that share the common goals of improving health outcomes, promoting health literacy and education and promoting research and initiatives that represent the diversity required to address the needs of all patients. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to . Find more information at Our online press service is just a click away: Follow us on Facebook: Follow us on Twitter: Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References: KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2022;120(suppl 5S):S1-S127. de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022:dci220027. doi:10.2337/dci22-0027 de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2022:S0085-2538(22)00634-2. doi: 10.1016/j.kint.2022.08.012. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; September 2022. ADA Professional Practice Committee. Addendum. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S144-S174. doi:10.2337/dc22-ad08 Blonde L, Umpierrez GE, McGill JB, et al. American Association of Clinical Endocrinology clinical practice guideline: developing a diabetes mellitus comprehensive care plan—2022 update. Endocr Pract. 2022;S1530-891X(22)00576-6. doi:10.1016/j.eprac.2022.08.002 Ruilope LM, Agarwal R, Anker S, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5)345-356. Kidney Disease: Improving Global Outcomes (KIDGO). The American Diabetes Association and Kidney Disease: Improving Global Outcomes release a consensus report on diabetes management in chronic kidney disease. Accessed October 2022. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi:10.1056/NEJMoa2110956 Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308. Breyer MD, Susztak K. Developing treatments for chronic kidney disease in the 21st century. Semin Nephrol. 2016;36(6):436-447. Anders HJ, Huber TB, Isermann B, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20. Bailey RA, Wang Y, Zhu V, et al. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7(1):415. doi:10.1186/1756-0500-7-415 KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3:1-150. American Diabetes Association. Standards of medical care in diabetes—2021. Diabetes Care. 2021;44(1):1-244. National Diabetes Statistics Report 2020: Estimates of Diabetes and Its Burden in the United States. Centers for Disease Control and Prevention. Accessed July 9, 2021. Stages of CKD. American Kidney Fund. Accessed May 11, 2021. United States Renal Data System. USRDS Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2020. Accessed November 2021.

New grade A recommendation in updated ADA Standards of Medical Care in Diabetes—2022 for KERENDIA® (finerenone) for improving cardiovascular (CV) outcomes and reducing risk of chronic kidney disease (CKD) progression in patients with CKD associated with type 2 diabetes (T2D)1 Update is based on evidence from more than 13,000 patients in largest cardiorenal outcomes Phase III program to investigate the occurrence of fatal and nonfatal CV events and progression of kidney disease in patients with CKD associated with T2D1,2 ADA and Kidney Disease: Improving Global Outcomes (KDIGO) orally presented a joint consensus statement that recommends use of finerenone for patients with T2D, an estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73m2, normal serum potassium concentration and albuminuria (ACR≥30 mg/g) despite maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor.3 The consensus statement is to be officially published in the coming months WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer’s KERENDIA® (finerenone) was recognized by the American Diabetes Association (ADA) Standards of Medical Care in Diabetes—2022 with a new grade A recommendation* for improving cardiovascular (CV) outcomes and reducing the risk of chronic kidney disease (CKD) progression in patients with CKD associated with type 2 diabetes (T2D).1 KERENDIA was approved in the United States based on the results of FIDELIO-DKD, to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, nonfatal myocardial infarction and hospitalization for heart failure in adult patients with CKD associated with T2D.4 The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.4 For more information, see Important Safety Information and the FIDELIO-DKD study results below. The addendum, titled Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2022, was updated based on evidence from the FIDELIO-DKD and FIGARO-DKD Phase III studies as well as the FIDELITY prespecified pooled analysis,1 which comprise the largest cardiorenal outcomes program to investigate the occurrence of fatal and nonfatal CV events and progression of kidney disease in patients with CKD associated with T2D in more than 13,000 patients. The program investigated the impact of finerenone in adults with CKD associated with T2D across a range of disease severity (CKD stages 1-4).2 The Standards of Medical Care in Diabetes—2022 were first released in December 2021 and included a grade A recommendation for KERENDIA in a new section emphasizing the importance of chronic kidney disease and risk management. At the ADA’s 82nd Scientific Sessions on June 6, and aligned with the ADA interim update, the ADA and Kidney Disease: Improving Global Outcomes (KDIGO) orally presented a joint consensus statement on the management of CKD and diabetes, recommending the use of finerenone for patients with T2D, an estimated glomerular filtration rate (eGFR) of ≥25 mL/min/1.73 m2, normal serum potassium concentration and albuminuria (albumin-to-creatinine ratio [ACR] ≥30 mg/g) despite maximum tolerated dose of renin-angiotensin-system (RAS) inhibitor.3 In the coming months, both the consensus statement and the final KDIGO update are expected to be published. “Managing patients with chronic kidney disease and type 2 diabetes requires a multidisciplinary care team that works together to control the disease while working to reduce the risk of cardiovascular events and slow kidney disease progression,” said Professor George Bakris, M.D., University of Chicago Medicine and principal investigator of FIDELIO-DKD. “The ADA and KDIGO—two highly respected clinical bodies—aligned on an oral joint consensus statement at the ADA scientific sessions supporting KERENDIA as a pillar of established therapy to improve cardiovascular and renal outcomes for patients with chronic kidney disease associated with type 2 diabetes.”3 “The joint statement orally presented at the ADA scientific sessions from two prestigious professional organizations provide additional clinical information for health care providers to consider when looking for treatment options in the ongoing management of their patients with chronic kidney disease associated with type 2 diabetes,” said Sameer Bansilal, M.D., M.S., FACC, Vice President, Cardiovascular, U.S. Medical Affairs at Bayer. “At Bayer, we are committed to continuing our long history of researching and providing treatments to fight cardiovascular and kidney diseases.” About the ADA Standards of Medical Care in Diabetes—2022 Update The new grade A recommendation reads: “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”1 Additionally, the “Lifestyle and Pharmacological Intervention” subsection now includes the following statement: “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”1 The December 2021 update included the following grade A recommendation for KERENDIA for CKD associated with T2D in section 11: “In patients with chronic kidney disease who are at increased risk for cardiovascular events or chronic kidney disease progression or are unable to use a sodium-glucose cotransporter 2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce chronic kidney disease progression and cardiovascular events (Table 9.2). A”5 The section was also updated to include evidence from the Phase III trial FIGARO-DKD and the prespecified pooled analysis FIDELITY, in addition to evidence from the Phase III trial FIDELIO-DKD.6 *Recommendations with an A rating, the ADA's highest recommendation, are based on large, well-designed clinical trials or well-done meta-analyses that have the best chance of improving outcomes. Generally, these recommendations have the best chance of improving outcomes when applied to the population to which they are appropriate.7 About KERENDIA (finerenone) INDICATION: KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D)4 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Concomitant use with strong CYP3A4 inhibitors4 Patients with adrenal insufficiency4 WARNINGS AND PRECAUTIONS: Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L4 Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium4 MOST COMMON ADVERSE REACTIONS: Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo: hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%), and hyponatremia (1.4% vs. 0.7%)4 DRUG INTERACTIONS: Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice4 Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate4 Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers4 USE IN SPECIFIC POPULATIONS: Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment4 Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B)4 Please read the Prescribing Information for KERENDIA. About Finerenone Phase III Clinical Trials Program Having randomized more than 13,000 patients with CKD associated with T2D around the world, the Phase III program with finerenone in CKD associated with T2D comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care (SoC) on both renal and CV outcomes.2 The FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study was a randomized, double-blind, placebo-controlled, multicenter study in adult patients with CKD associated with T2D, defined as either having an uACR of 30 to 300 mg/g, eGFR 25 to 60 mL/min/1.73 m2 and diabetic retinopathy, or as having an uACR of ≥300 mg/g and an eGFR of 25 to 75 mL/min/1.73 m2.4,8 The trial excluded patients with known significant nondiabetic kidney disease and a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (NYHA class II to IV).4 All patients were to have a serum potassium ≤4.8 mEq/L at screening and be receiving standard of care background therapy, including a maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).4 A total of 5,674 patients were randomized to receive finerenone (N=2,833) or placebo (N=2,841) and were followed for a median of 2.6 years.4 The mean age of the study population was 66 years, and 70% of patients were male.6 The trial population was 63% white, 25% Asian, and 5% Black.4 Finerenone reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥40%, kidney failure, or renal death (HR 0.82 [95% CI, 0.73-0.93; P=0.001]).4 The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.6 There were few renal deaths during the trial.4 Finerenone also reduced the incidence of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure (HR 0.86 [95% CI, 0.75-0.99; P=0.034]).4 The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.4 The most frequently reported adverse reaction was hyperkalemia (18.3% KERENDIA vs. 9% placebo).4 Hospitalization due to hyperkalemia for the KERENDIA group was 1.4% versus 0.3% in the placebo group.4 Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving KERENDIA versus 0.9% of patients receiving placebo.4 FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,352 participants to finerenone (N=3686) or placebo (N=3666) on top of standard of care, including a maximum tolerated labeled dose of ACEis or ARBs.9 Patients had UACR ≥30–<300 mg/g and eGFR ≥25–≤90 mL/min/1.73m2 or UACR ≥300–≤5000 mg/g and eGFR ≥60 mL/min/1.73m2.9 This data is under review with the FDA. KERENDIA significantly reduced the risk of the composite primary endpoint of time to first occurrence of CV death or nonfatal CV events (myocardial infarction, stroke or heart failure hospitalization) by 13% (relative risk reduction, HR 0.87 [95% CI, 0.76-0.98; P=0.0264]) over a median duration of follow-up of 3.4 years when added to maximum tolerated labeled dose of ACEi or ARB in adults with CKD associated with T2D.9 The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure.9 The incidence of the secondary endpoint, a composite of time to kidney failure, a sustained decrease of eGFR ≥40% from baseline over a period of at least four weeks, or renal death, was lower with finerenone than with placebo, affecting 350 (9.5%) and 395 (10.8%) patients, respectively.8 However, the difference was not statistically significant (HR 0.87 [95% CI, 0.76-1.01]) over a median duration of follow-up of 3.4 years.9 Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).9 Hospitalization due to hyperkalemia for the finerenone group was 0.6% versus 0.1% in the placebo group, and there was no hyperkalemia-related death in either treatment group. Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.9 Bayer also initiated the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III study that will investigate finerenone compared to placebo in more than 5,500 symptomatic heart failure patients (NYHA class II-IV) with a left ventricular ejection fraction of ≥40%.10 The primary objective of the study is to demonstrate superiority of finerenone over placebo in reducing the rate of the composite endpoint of cardiovascular death and total (first and recurrent) heart failure events (defined as hospitalizations for heart failure or urgent heart failure visits).10 About Chronic Kidney Disease Associated With Type 2 Diabetes Patients with CKD associated with T2D are three times more likely to die from a CV-related cause than those with T2D alone.11 CKD is a serious and progressive condition that is generally underrecognized.12 CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.13-15 Approximately 40% of all patients with T2D develop CKD.15 Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.13,14,16,17 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.18-20 About Bayer’s Commitment in Cardiovascular and Kidney Diseases Bayer is an innovation leader in the area of cardiovascular diseases, with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. The heart and the kidneys are closely linked in health and disease, and Bayer is working in a wide range of therapeutic areas on new treatment approaches for cardiovascular and kidney diseases with high unmet medical needs. The cardiology franchise at Bayer already includes a number of products and several other compounds in various stages of preclinical and clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cardiovascular diseases are treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to . Find more information at Our online press service is just a click away: Follow us on Facebook: Follow us on Twitter: Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References: ADA Professional Practice Committee. Addendum. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S144-S174. doi:10.2337/dc22-ad08 Ruilope LM, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5)345-356. Rossing P. Consensus—new joint statement from the ADA and KDIGO on management of diabetes and CKD. Presented at: ADA 82nd Scientific Sessions; June 6, 2022. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021. American Diabetes Association Professional Practice Committee. 11. Chronic kidney disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2021;45(suppl 1). doi:10.2337/dc22-s011 American Diabetes Association Professional Practice Committee. Addendum. 11. Chronic kidney disease and risk management: Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S175-S184. doi:10.2337/dc22-ad08a American Diabetes Association Professional Practice Committee. Chronic kidney disease and risk management: standards of medical care in diabetes—2017. Diabetes Care. 2017;40(Suppl 1):S1–S2. Bakris G, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229. Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;10.1056/NEJMoa2110956. doi:10.1056/NEJMoa2110956 ClinicalTrials.gov. Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity & Mortality in Participants with Heart Failure and Left Ventricular Ejection Fraction Greater or Equal to 40% (FINEARTS-HF). 2020. Accessed November 2021. Afkarian M, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308. Breyer MD, et al. Developing treatments for chronic kidney disease in the 21st Century. Semin Nephrol. 2016;36(6):436-447. Anders HJ, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377. Thomas MC, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20. Bailey R, et al. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7(1):415. doi:10.1186/1756-0500-7-415. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3:1-150. American Diabetes Association. Standards of medical care in diabetes—2021. Diabetes Care. 2021;44(1):1-244. National Diabetes Statistics Report 2020: Estimates of Diabetes and Its Burden in the United States. Centers for Disease Control and Prevention. Accessed July 9, 2021. Stages of CKD. American Kidney Fund. Accessed May 11, 2021. United States Renal Data System. USRDS Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2020. Accessed November 2021. COR-KER-US-0018-2