ADA Updates on Finerenone, SGLT2 Inhibitors, and Race-Based eGFR

As it gears up for the first in-person Scientific Sessions for 3 years, the American Diabetes Association (ADA) has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.

• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

• The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online May 31 in Diabetes Care.

CVD and Risk Management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “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”

• “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.”

• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. A”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate…is ongoing,” because that trial investigating pemafibrate (Kowa Company), a novel selective peroxisome proliferator-activated receptor alpha (PPARα) modulator (or fibrate), has been discontinued.

Chronic Kidney Disease and Risk Management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred…Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to revamp the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the US.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation).

• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence From Clinical Trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)

• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD

• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)

• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)

• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT)

Diabetes Care. Published online May 31, 2022. Addendum. 10, Addendum. 11

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