Finerenone Lowers Albuminuria in Type 1 Diabetes with CKD: FINE‑ONE Phase III Shows 25% Average UACR Reduction and Acceptable Safety

Article structure

This article is organized to (1) summarize the clinical need in type 1 diabetes (T1D) with chronic kidney disease (CKD); (2) describe the FINE‑ONE trial design; (3) present and interpret primary efficacy and safety data; (4) place findings in context of existing evidence and biologic rationale; and (5) discuss clinical implications, limitations, and next steps.

Highlights

• FINE‑ONE is a randomized, double‑blind Phase III trial in 242 adults with T1D and CKD that met its primary endpoint: finerenone reduced UACR by an average of 25% versus placebo over 6 months (P = .0001).
• UACR reductions were detectable at 3 months (30% vs 10% placebo) and increased at 6 months (37% vs 13%); effects were consistent across prespecified subgroups.
• Safety profile was similar to prior T2D CKD trials: overall adverse event rates were comparable, with a higher incidence of hyperkalemia (10.1% vs 3.3%) but low discontinuations (1.7%).

Background: disease burden and unmet need

Chronic kidney disease remains a major complication of type 1 diabetes. Despite improvements in glycemic control and multidisciplinary care, contemporary estimates indicate up to 30% of people with T1D develop CKD in their lifetime, with prevalence rising substantially with age. CKD in diabetes is the leading pathway to kidney failure and is strongly associated with cardiovascular morbidity and mortality.

Therapeutic progress for CKD has accelerated in the past decade, primarily in people with type 2 diabetes (T2D)—with agents such as SGLT2 inhibitors and the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone demonstrating kidney and cardiovascular benefits. However, landmark evidence guiding pharmacologic prevention and treatment of CKD specifically in T1D has been relatively static since early trials in the 1990s, creating an unmet need for contemporary, T1D‑specific data. Many effective therapies in T2D either lack formal indication in T1D (for example, SGLT2 inhibitors and certain GLP‑1 receptor agonists) or are used off label with safety concerns (notably increased risk of diabetic ketoacidosis with SGLT2 inhibitors in insulin‑dependent patients).

Study design: FINE‑ONE (NCT05901831)

FINE‑ONE (FINErenone efficacy and safety in chronic kidney disease and type ONE diabetes) is a global, randomized, double‑blind, placebo‑controlled Phase III trial designed to evaluate finerenone added to standard of care in adults with T1D and CKD. The trial enrolled 242 participants across 82 centers in nine countries. Key eligibility criteria included:

• Type 1 diabetes (insulin treated) with A1c < 10%.
• UACR ≥ 200 to < 5000 mg/g.
• Estimated glomerular filtration rate (eGFR) ≥ 25 to < 90 mL/min/1.73 m2.
• Serum potassium ≤ 4.8 mmol/L at baseline.

Most participants were receiving stable renin–angiotensin system (RAS) blockade at randomization. Participants were randomized 1:1 to once‑daily finerenone (10 or 20 mg per investigator titration) or matching placebo. The primary endpoint was the relative change in UACR from baseline averaged over 3 and 6 months; UACR was prespecified as a bridging biomarker for kidney‑outcome benefit, based on prior finerenone data in T2D and established associations between reductions in albuminuria and long‑term kidney outcomes.

Key findings: efficacy

FINE‑ONE met its primary endpoint. The main efficacy results are:

• At 3 months: mean reduction in UACR was 30% with finerenone vs 10% with placebo (between‑group difference ≈ 21%).
• At 6 months: mean reduction in UACR was 37% with finerenone vs 13% with placebo (between‑group difference ≈ 28%).
• Primary analysis (average of 3 and 6 months): least squares geometric mean ratio over 6 months was 0.75, corresponding to a 25% reduction in UACR versus placebo (P = .0001).
• Effects were consistent across prespecified subgroups including age strata, sex, baseline eGFR and baseline albuminuria.

Interpretation: The magnitude and early onset of UACR lowering mirror observations from finerenone trials in T2D (FIDELIO‑DKD, FIGARO‑DKD and pooled FIDELITY analyses), supporting biological plausibility that mineralocorticoid receptor overactivation contributes to kidney disease progression in T1D as well as T2D. The trial used UACR as a surrogate endpoint—a practical and accepted strategy for bridging evidence in populations where large, long outcome trials may be logistically challenging.

Key findings: safety and tolerability

Overall safety in FINE‑ONE was similar between groups:

• Treatment‑emergent adverse events (TEAEs): 47.1% finerenone vs 49.2% placebo.
• Treatment‑emergent serious adverse events (TESAEs): 11.8% finerenone vs 11.5% placebo.
• Hyperkalemia (adverse event of special interest): 10.1% finerenone vs 3.3% placebo.
• Treatment discontinuation due to hyperkalemia: 1.7% finerenone vs 0% placebo.

These findings are consistent with prior experience of finerenone in large T2D CKD trials, where modest increases in serum potassium and hyperkalemia were observed but with low rates of permanent discontinuation when monitoring protocols were followed.

Biologic rationale and mechanistic insights

Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist that reduces mineralocorticoid receptor‑mediated inflammation and fibrosis in the heart and kidney. Overactivation of the mineralocorticoid receptor promotes glomerular and tubulointerstitial damage, and blocking this pathway has shown kidney‑protective effects in preclinical models and in clinical trials in T2D. The UACR reductions seen in FINE‑ONE provide mechanistic coherence: albuminuria reflects glomerular–tubular barrier dysfunction and is a modifiable risk marker correlated with long‑term kidney and cardiovascular outcomes.

Context with prior evidence

Key trials of finerenone in T2D with CKD include FIDELIO‑DKD and FIGARO‑DKD (both randomized Phase III trials) and pooled analyses (FIDELITY) demonstrating reductions in kidney‑ and cardiovascular‑outcome composites. Large randomized trials of SGLT2 inhibitors have also demonstrated kidney protection in people with CKD, but many of these enrolled predominantly or exclusively people with T2D. Contemporary management guidelines for diabetic kidney disease emphasize RAS blockade, SGLT2 inhibition (where indicated), blood pressure control, lipid management and individualized glycemic targets; however, formal guideline guidance specific to T1D populations has been limited by lack of T1D‑specific outcome data. FINE‑ONE fills an important evidence gap by directly studying finerenone in T1D with CKD.

Expert commentary and limitations

The principal investigators and external nephrology experts have highlighted the clinical importance of bringing new therapies to people with T1D and CKD, noting FINE‑ONE is the first positive Phase III finerenone study in T1D since pivotal RAS work in the 1990s. Specific points to consider:

• Surrogate endpoint: UACR is a validated risk marker and accepted as a bridging biomarker for kidney disease trials, but it is not a clinical outcome (e.g., progression to kidney failure or sustained eGFR decline). Long‑term outcome data in T1D are needed to confirm that UACR lowering translates into reductions in hard kidney and cardiovascular events in this population.
• Duration and size: FINE‑ONE’s 6‑month primary period and 242 participants are appropriate for a biomarker‑bridging trial but cannot replace large, long‑term outcome trials. The sample size and trial duration limit assessment of rare safety events and long‑term efficacy.
• Generalisability: Participants had UACR ≥200 mg/g and eGFR ≥25 mL/min/1.73 m2; applicability to people with microalbuminuria below that threshold, or with eGFR <25 mL/min/1.73 m2, is uncertain.
• Hyperkalemia and monitoring: The increased incidence of hyperkalemia requires clinical vigilance and serum potassium monitoring when finerenone is used, particularly in the context of background RAS blockade or concomitant agents that increase potassium.
• Concomitant therapies: Many guideline‑recommended agents for T2D CKD (SGLT2 inhibitors) are not formally indicated in T1D and may carry distinct safety considerations in insulin‑treated patients. How finerenone will be positioned among available and emerging agents for T1D CKD requires future study and guideline deliberation.

Clinical implications and next steps

The FINE‑ONE results support finerenone as a promising therapeutic option to reduce albuminuria in people with T1D and CKD, with a safety profile consistent with prior trials. Regulatory actions are anticipated: the sponsor (Bayer) has indicated plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration in 2026 based on these findings.

Important next steps include:

• Longer‑term follow‑up or dedicated outcome trials in T1D to confirm that UACR reductions translate into fewer hard kidney and cardiovascular events.
• Post‑marketing and real‑world safety surveillance focusing on hyperkalemia risk and drug interactions in diverse T1D populations.
• Studies to define optimal sequencing or combination strategies with other kidney‑protective agents, especially where SGLT2 inhibitors may be considered on an individualized basis in T1D.
• Cost‑effectiveness analyses and guideline deliberations to integrate finerenone into clinical practice for T1D CKD if regulatory approvals follow.

Conclusion

FINE‑ONE provides the first Phase III evidence in decades that a nonsteroidal MRA can reduce albuminuria in adults with type 1 diabetes and chronic kidney disease. The trial demonstrated a statistically robust and clinically meaningful average UACR reduction of 25% versus placebo over six months and a tolerability profile similar to that observed in T2D trials, with an expected increase in hyperkalemia events that was manageable. While UACR is a validated surrogate and the results are compelling, confirmation that these changes will produce long‑term reductions in kidney failure and cardiovascular events in T1D will require further data. For clinicians caring for people with T1D and CKD, FINE‑ONE is an important advance that justifies careful consideration of finerenone pending regulatory decisions and provides impetus for subsequent outcome research.

Funding and trial registration

FINE‑ONE was sponsored by Bayer, the manufacturer of finerenone (KERENDIA). ClinicalTrials.gov identifier: NCT05901831. Bayer has indicated plans for a supplemental New Drug Application to the U.S. FDA in 2026 based on these data.

Selected references

1. FINE‑ONE (FINErenone efficacy and safety in chronic kidney disease and type ONE diabetes). ClinicalTrials.gov Identifier: NCT05901831.
2. Finerenone in patients with chronic kidney disease and type 2 diabetes: FIDELIO‑DKD and FIGARO‑DKD randomized controlled trials; pooled FIDELITY analyses (key phase 3 evidence supporting finerenone in T2D CKD). See: NEJM 2021 (FIDELIO‑DKD, FIGARO‑DKD) and pooled analyses published subsequently.
3. The Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the development and progression of long‑term complications in insulin‑dependent diabetes mellitus. N Engl J Med. 1993; (DCCT landmark evidence shaping T1D care).
4. DAPA‑CKD Trial Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020; (key evidence for SGLT2 inhibitors in CKD populations, predominantly T2D).
5. KDIGO Clinical Practice Guidelines for Diabetes Management in CKD. Kidney Int. 2022; (guideline context for CKD management and use of kidney‑protective therapies).

Note: Reference list includes major, peer‑reviewed trials and guideline documents relevant to the mechanism, comparative evidence, and the rationale for using albuminuria as a bridging biomarker. Readers should consult original trial publications (FIDELIO‑DKD, FIGARO‑DKD, FIDELITY pooled analyses) and up‑to‑date guideline statements for further detail.