HOUSTON — The nonsteroidal mineralocorticoid-receptor antagonist drug finerenone led to significant reductions in albuminuria in patients with type 1 diabetes (T1D) and chronic kidney disease (CKD) compared to placebo, in groundbreaking findings presented here at Kidney Week 2025: American Society of Nephrology’s Annual Meeting.

In addition, finerenone was generally well tolerated in the population; safety and tolerability were consistent with safety observed in patients with type 2 diabetes (T2D) and CKD.

This is the first work in T1D in over three decades that has shown “a beneficial risk profile for patients that will likely translate into long-term kidney protection and possibly also cardiovascular disease prevention,” said first author Hiddo J. Heerspink, MD, from the University Medical Center Groningen, the Netherlands, who presented the late-breaking findings.

Despite improvements in care over the years for T1D, as many as 30% of all patients — and up to 50% of patients aged 60 years or older — develop CKD, also increasing the risk for cardiovascular disease, Heerspink noted.

While a slew of new therapies has emerged in the past decade for the treatment of CKD in patients with type 2 diabetes, “the medical management of type 1 diabetes and chronic kidney disease is still based on evidence from 1993, when RAS [renin-angiotensin system] inhibition was demonstrated to be effective and safe,” Heerspink said. 

“So, while the treatment for type 2 diabetes has advanced, we have left the type 1 diabetes patients behind,” he added. “This illustrates a clear unmet need for these patients.” 

Medications such as GLP-1 receptor agonists and SGLT2 inhibitors indicated for T2D are not currently indicated for T1D, although they are being increasingly prescribed. Finerenone, another recent addition to the T2D armamentarium, addresses the overactivation of the mineralocorticoid receptor, which is a key factor in the progression of CKD in T1D as well as in T2D.

Significant Differences Already Observed at 3 Months

To investigate the possible benefits of finerenone in T1D, Heerspink and colleagues conducted the phase 3, double-blind FINE-ONE trial, enrolling 242 patients at 82 centers across nine countries. The mean age of patients was 52 years and 65% were male; the mean duration of diabetes was 32 years. 

All patients had CKD, defined as urinary albumin creatinine ratio (UACR) of ≥ 200 to < 5000 mg/g; an estimated glomerular filtration rate (eGFR) between ≥ 25 and < 90 mL/min/1.73 m²; T1D, with an A1c of < 10%; and serum potassium of ≤ 4.8 mmol/L.

Most patients were receiving stable RAS therapy. They were randomized 1:1 to treatment either with finerenone (10 or 20 mg once daily) or placebo.

At 3 months, significant differences between the groups were already observed, with a reduction in UACR from baseline of 30% with finerenone vs 10% with placebo, for a difference of 21%. At 6 months, the finerenone group had a reduction of 37% vs 13% in the placebo group, for a difference of 28%. 

The study met its primary endpoint, which was the average between the 3 and 6 months, with a least squares geometric mean ratio over 6 months of 0.75, or a reduction of 25% (P = .0001).

“This effect is robust and clinically meaningful because we know from clinical trials that a 25% reduction in albuminuria is associated with a very high likelihood of a long-term reduced risk of dialysis and kidney transplantation,” Heerspink said.

Treatment-emergent adverse events (TEAEs) occurred in 47.1% of those treated with finerenone and 49.2% for placebo, and rates of serious TEAEs were also similar, at 11.8% and 11.5%, respectively. 

Hyperkalemia, a known side effect of finerenone, was observed more frequently with the drug, at 10.1% compared to placebo (3.3%). However, Heerspink noted that “the clinical impact of these events was low,” with only 1.7% having treatment discontinuation due to hyperkalemia, vs 0% with placebo.

He added that the benefits observed with finerenone were observed across all the study’s prespecified subgroups — including across age groups, male or female, higher or lower eGFR, and higher or lower albuminuria — and the effects were consistent.

These results indicate that “finerenone is a novel therapeutic option with a favorable benefit–risk profile that may reduce adverse kidney outcomes in people with chronic kidney disease and type 1 diabetes,” Heerspink concluded.

Asked why albuminuria was used as the trial’s outcome, Heerspink explained that with CKD representing a late manifestation of T1D, large studies of several thousand patients are not possible. And with previous studies of finerenone in T2D showing the endpoint benefits to be explained by the reduction in albuminuria, it was determined to represent a ‘bridging biomarker’ sufficient to translate evidence from T2D to T1D.

In a press release, Bayer noted that plans are underway to submit a supplemental New Drug Application to the US Food and Drug Administration in 2026 based on the results of the trial. 

In the meantime, Heerspink noted that finerenone is already being used in clinical practice around the world. “It would be off-label in the US, but the drug is available to try,” if clinicians were inclined.

Next Step: Preventing Progression?

Commenting to Medscape Medical News, Nirupama Ramkumar, MD, MPH, an associate professor of internal medicine at the University of Utah Health in Salt Lake City, agreed that the findings are important.

“I think the study is very impactful because the number of agents that we can use currently in type 1 diabetes is very limited,” she said. 

“We've only tested the renin-angiotensin system (RAS) inhibitors, and for 35 years we've really had no other medications available, so this is definitely groundbreaking.

Right now, we just say ‘manage your blood pressure,’ or ‘manage your diabetes,’ so I think it’s very exciting.

“We also are always concerned about side effects and there are differences in effects between type 1 and type 2 diabetes, so it’s good to see these results.”

Ramkumar added that “a next step would be to see if we can prevent patients like this from progressing with finerenone,” she said.

The study was funded by Bayer. 

Heerspink reported consulting and/or other relationships with AstraZeneca, Alexion, Amgen, Bayer, Boehringer Ingelheim, Dimerix, Eli Lilly, Novartis, NovoNordisk, Roche, and Travere Therapeutics. Ramkumar reported no relevant financial relationships.