Finerenone Reduces T2D Onset in HF With Preserved EF

MADRID, Spain — The nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone reduced the incidence of new-onset type 2 diabetes by approximately 25% in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), according to a prespecified subgroup analysis of the FINEARTS-HF trial.

This is “very exciting, and quite a bonus treatment benefit on top of improvement in symptoms of heart failure,” said John McMurray, MD, BHF Centre of Research Excellence for Heart Failure Prevention and Treatment, University of Glasgow, and Queen Elizabeth University Hospital, Glasgow, Scotland.

As previously reported by Medscape Medical News, the FINEARTS-HF trial showed that finerenone reduced the primary endpoint of worsening heart failure events and death from cardiovascular causes by 16% compared with placebo (rate ratio, 0.84; P = .007).

McMurray presented the results of the subgroup analysis — which looked at the impact of finerenone in patients with HFmrEF/HFpEF with and without type 2 diabetes — at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Overall trial results were published on September 1, 2024, in The New England Journal of Medicine.

Finerenone has different physiochemical properties from steroidal MRAs and has been shown in two large trials (FIGARO-DKD and FIDELIO-DKD) to reduce cardiovascular and kidney outcomes in patients with type 2 diabetes and chronic kidney disease.

Explaining the significance of finenerone’s effectiveness in patients with diabetes, McMurray pointed out that people with type 2 diabetes and heart failure had worse outcomes than people without diabetes. “Interestingly, this excess risk is relatively larger in patients with HFmrEF/HFpEF than [those with] HFrEF,” he reported. 

“But,” he added, “we were interested to see whether finerenone would be as effective in patients without diabetes, because the only large trials to date have been in people who have the disease. And we found that it was.”

FINEARTS-HF was a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that finerenone would reduce cardiovascular death and total worsening heart failure events in 6016 patients with heart failure and a left ventricular ejection fraction of at least 40%.

Patients were randomly assigned to receive finerenone (20 mg or 40 mg once daily) or placebo. Most patients were in New York Heart Association functional class II heart failure. The primary endpoint of the trial was cardiovascular death and total worsening of heart failure events, which included hospitalizations for heart failure or urgent heart failure visits. 

The current analysis grouped patients according to baseline diabetes status — that is, those with and those without type 2 diabetes. There were 3222 patients without diabetes at baseline; 1606 of them were treated with finerenone, and 1616 were given placebo. 

In patients with an A1c value ≥ 6.5% at two consecutive follow-up visits, or in whom therapy was initiated with glucose-lowering drugs other than sodium-glucose cotransporter 2 (SGLT2) inhibitors, 9.1% of those receiving placebo experienced new-onset diabetes compared with 7.2% of those receiving finerenone (hazard ratio [HR], 95% CI, 0.75; 0.59-0.96; P = .024).

This was a significant reduction and a very exciting finding for multiple reasons, said McMurray. “People with heart failure have a very high incidence of type 2 diabetes; developing type 2 diabetes on top of heart failure is a disaster; and, finally, the older steroidal MRA spironolactone seems to increase A1c” and is therefore metabolically ‘unfriendly.'”

The reduction in new-onset diabetes was consistent regardless of whether SGLT2 inhibitors were included or excluded, remarked McMurray, accommodating for the fact that some patients may have received these drugs for heart failure. 

In addition, the relative risk reduction in the primary composite endpoint of the trial “was consistent in those with diabetes and without diabetes…across the range of A1c at baseline,” he reported. 

Overall, finerenone was well tolerated, with a similar number of serious adverse events in both the finerenone and placebo groups. 

With finerenone, “we saw more hyperkalemia, but less hypokalemia,” said McMurray. Notably, there were very few episodes of hyperkalemia that lead to hospitalization; cases occurred in 16 patients in the finerenone arm and six in the placebo arm, none of which led to death. 

Commenting on the results, co-moderator Ellen Vercalsteren, PhD, from Karolinska Institutet, Stockholm, Sweden, who specializes in diabetes and cardiology research, said, “It’s exciting to see that finerenone works on the kidneys and in heart failure while also reducing the risk of diabetes.” 

“It’s also interesting that it works in both preserved ejection fraction and reduced ejection fraction, because they have different etiologies,” she added. 

“It reminds me of SGLT2 inhibitors, that also have this abundance of properties,” Vercalsteren told Medscape Medical News. 

She’s curious to see what will come next. Will it be effective in treating diabetes or just for risk prevention? Vercalsteren wondered. 

There were no treatment options for heart failure until SGLT2 inhibitors, she noted. “This seems like the next step to finally helping a group of patients very much in need.” 

The FINEARTS-HF trial was funded by Bayer. Glasgow University received funds from Bayer for McMurray’s time as trial investigator and for the statistical analysis presented here at EASD. He represented the trial on behalf of the FINEARTS-HF committees and investigators. Vercalsteren has declared no relevant financial disclosures.