"F" is for Fighting for the Future of Those With Diabetic Kidney Disease

Volume 12, Issue 2

Diabetes remains a leading cause of chronic kidney disease (CKD), which often progresses to advanced stages and hemodialysis in a significant number of patients. Commonly prescribed agents like ACE inhibitors and angiotensin receptor blockers (ARB), while effective in slowing progression, cannot prevent a significant number of patients with CKD from progressing into the more advanced stages.

In this week’s issue of Talking Therapeutics, we explore a recently approved agent with some promising data in patients with diabetic CKD.

Point 1: "F" is for Finerenone

The FIDELIO-CDK study was aimed at evaluating the role of fineronone in slowing CKD progression and reducing mortality. Overactivation of the mineralocorticoid receptor has been linked to CKD, diabetes, and other cardiorenal diseases due to an increase in inflammation and fibrosis, which in turn affect the kidneys and heart, authors noted. Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist that has shown greater efficacy in reducing inflammation and fibrosis compared to steroidal agents such as spironolactone and eplerenone.

In this study, more than 5000 patients with advanced CKD and type 2 diabetes were randomly assigned to receive finerenone or placebo. The finerenone group saw a significant reduction in “the primary composite outcome of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes” compared to placebo (17.8% vs 21.1%, [HR, .82; 95% CI, .73-.93; P=.001]).

Importantly, death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure was also reduced with finerenone. All patients in this trial were maximized on ACE inhibitor or ARB therapy as background.

The follow-up trial FIGARO-DKD—which was done in patients with type 2 diabetes and less severe CKD—similarly found a reduction in adverse cardiovascular events, which was driven by a reduction in hospitalization for heart failure (HR, .71; 95% CI, .56-.9). Unlike FIDELIO-DKD, FIGARO-DKD did not find a reduction in adverse renal endpoints.

Hyperkalemia-related discontinuation occurred in 1.2% of patients receiving finerenone and .4% of those in the placebo group, but the risk of treatment-related adverse events was overall low.

Point 2: Does "F" Spell the Final Story?

The results of FIDELIO and FIGARO are compelling, and the FDA recently granted finerenone the indication 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 CKD and type 2 diabetes.

Despite these impressive data and the new FDA indication, finerenone isn’t the only game in town. In the DAPA-CKD trial, the SGLT2 inhibitor dapagliflozin was found to reduce the primary outcome, which was “a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes” in patients with CKD with or without diabetes. As a result, dapagliflozin is now indicated to reduce the risk of sustained eGFR decline, end‑stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of progression.

So the million dollar question is: how would finerenone stack up against dapagliflozin in a head-to-head trial of patients with CKD? Unfortunately, at least for now, that question remains unanswered.