New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.
The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.
Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.
Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.
Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.
For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.
‘A lot of interest in finerenone’ in U.S.
“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.
The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.
But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.
The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.
He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.
The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”
Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.
“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.
Finerenone has also been recently approved in the European Union.