European Association for the Study of Diabetes

European Association for the Study of Diabetes

Source:

McGill J. Finerenone: A new approach to kidney protection in patients with type 2 diabetes. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 27-Oct. 1, 2021 (virtual meeting).

Disclosures: McGill reports receiving advisory and consultant fees or grants from Bayer, Beta Bionics, Boehringer Ingelheim, Dexcom, Eli Lilly, MannKind Corp., Medtronic, Metavant, Novo Nordisk, Provention Bio and Salix.
October 05, 2021
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Finerenone plus SGLT2 inhibition may yield additive CV, kidney benefits: FIGARO-DKD

Source:

McGill J. Finerenone: A new approach to kidney protection in patients with type 2 diabetes. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 27-Oct. 1, 2021 (virtual meeting).

Disclosures: McGill reports receiving advisory and consultant fees or grants from Bayer, Beta Bionics, Boehringer Ingelheim, Dexcom, Eli Lilly, MannKind Corp., Medtronic, Metavant, Novo Nordisk, Provention Bio and Salix.
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The nonsteroidal mineralocorticoid receptor antagonist finerenone provides cardiovascular and kidney benefits in adults with diabetic kidney disease independent of and combined with SGLT2 inhibitors, new analyses show.

Janet B. McGill

Available data from the FIGARO-DKD trial — which included participants with and without background SGLT2 inhibitor therapy — show finerenone (Kerendia, Bayer) reduced CV events and slowed chronic kidney disease progression vs. placebo, irrespective of SGLT2 inhibitor use at baseline or at any time during the trial, according to Janet B. McGill, MD, professor of medicine at Washington University School of Medicine in St. Louis, and an Endocrine Today Editorial Board Member. Sub-analyses conducted to explore the treatment effect of finerenone in patients with and without SGLT2 inhibitor use at baseline also showed additive benefits of SGLT2 inhibition, McGill said.

Finerenone added to a SGLT2 inhibitor provided more CV and renal benefits than finerenone alone. Data were derived from McGill J. Finerenone: A new approach to kidney protection in patients with type 2 diabetes. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 27-Oct. 1, 2021 (virtual meeting).

“SGLT2 inhibitors have proven benefit in persons with either CKD or heart failure and prevent major adverse CV events in persons with atherosclerotic CVD,” McGill told Healio. “It is important to understand how newer agents, like finerenone, will work in patients taking an SGLT2 inhibitor, as more and more patients are being treated with them.”

Assessing combination treatment

In FIDELIO-DKD, researchers observed a 25% reduction in urinary albumin-to-creatinine ratio among participants assigned finerenone and prescribed an SGLT2 inhibitor at baseline, compared with a 32% reduction among those who received finerenone and were not taking an SGLT2 inhibitor at baseline. However, the subgroup of participants prescribed SGLT2 inhibitors was small, making up just 4.6% of the cohort, McGill said.

“Due to the low numbers, it was not possible to make meaningful conclusions from this trial,” McGill said during a virtual presentation at the European Association for the Study of Diabetes annual meeting.

Preclinical data suggested combination therapy with finerenone and the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) offers benefits over monotherapy with either agent, McGill said.

“In an animal, preclinical model of hypertension-induced end-organ damage, the combination therapy showed equivalence to high-dose finerenone and greater reduction than empagliflozin alone,” McGill said. “When cardiofibrosis was analyzed, the combination [therapy] again showed less cardiac fibrosis than either drug given in monotherapy. This is clearly shown as a survival benefit.”

A sub-analysis was performed to explore the treatment effect of finerenone for patients with and without SGLT2 inhibitor use at baseline in FIGARO-DKD, where SGLT2 use was permitted at any time during the trial. At baseline, 8.4% of participants were prescribed SGLT2 inhibitors; these participants were also older, had a higher estimated glomerular filtration rate, and were more likely to be taking statins and GLP-1 receptor agonists, McGill said.

Improvements in albuminuria, renal decline

In FIGARO-DKD, researchers observed a greater improvement in urinary albumin-to-creatinine ratio among participants assigned finerenone with background SGLT2 inhibitor therapy vs. those assigned finerenone without SGLT2 therapy (41% vs. 32%; P = .04 for interaction).

CV benefit seen with finerenone use was consistent irrespective of baseline SGLT2 inhibitor use during the trial, with an HR for the composite CV outcome of 0.87 for the overall population (95% CI, 0.76-0.98), 0.89 for those assigned finerenone without background SGLT2 use (95% CI, 0.78-1.01) and 0.49 for those who received finerenone with background SGLT2 use (95% CI, 0.28-0.86).

Renal benefit was similarly consistent irrespective of SGLT use at baseline and during the trial. In the overall population, HR for the composite kidney endpoint, including a 40% drop in eGFR, was 0.87 for the overall population (95% CI, 0.76-1.01), 0.88 for those assigned finerenone without background SGLT2 use (95% CI, 0.76-1.03), and 0.7 for those who received finerenone with background SGLT2 use (95% CI, 0.37-1.3). When the composite kidney outcome included an eGFR decrease of at least 57%, HRs favoring finerenone vs. placebo were 0.77 for the overall population (95% CI, 0.6-0.99), 0.8 for no SGLT2 use (95% CI, 0.62-1.04) and 0.51 for those prescribed SGLT2 therapy (95% CI, 0.18-1.43).

“I was surprised that finerenone seemed to have greater benefit for CV and renal composite outcomes when used in patients taking SGLT2 inhibitor than it did in those not taking an SGLT2 inhibitor,” McGill told Healio. “Additional information will become available with publication of the FIDELITY meta-analysis, that will combine the datasets from FIGARO and FIDELIO. The data show finerenone is the newest agent that provides cardio-renal protection for persons with type 2 diabetes and evidence of CKD. It can be used across a broad cohort of patients, from mild to more severe CKD, and with or without the anti-diabetes agents that have proven CV or renal benefit.”