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Key result
Finerenone reduces CV and kidney events and increases CKM syndrome regression ~66% versus placebo.
- n=12,990
Why the study?
Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of obesity, diabetes, CKD, and CVD. This study evaluated the efficacy and safety of finerenone across CKM stages, as well as its effects on CKM syndrome progression and regression over time.
Does finerenone reduce cardiovascular and kidney events and improve CKM syndrome regression in patients with type 2 diabetes and chronic kidney disease across CKM stages?
Key Points
- This study evaluates the efficacy and safety of finerenone in reducing cardiovascular and kidney events across stages of cardiovascular-kidney-metabolic syndrome.
- Post hoc pooled analysis of 2 randomized, double-blind, placebo-controlled trials (FIDELITY) involving 12,990 participants from 48 countries.
- Patients with type 2 diabetes and chronic kidney disease classified into CKM syndrome stages based on American Heart Association criteria.
- Participants received either finerenone or placebo, with outcomes measured over a median follow-up of 3 years.
- Stage 4 CKM syndrome participants had higher rates of cardiovascular (aHR 1.87, 95% CI 1.56-2.24) and kidney events (aHR 1.96, 95% CI 1.43-2.69) compared to stage 2.
- Finerenone reduced cardiovascular events by -1.1 per 100 person-years in stage 4 and -0.4 in stage 2.
- After 3 years, finerenone users were more likely to experience CKM syndrome regression (11.4% vs 7.4%; aOR 1.66, 95% CI 1.30-2.13; P < .001) and less likely to see CKM progression (aOR 0.89, 95% CI 0.79-1.00; P = .05).
Study Design
Type
RCT (n=12,990)
Blinding
double-blind
Randomization
randomly assigned
Multicenter
Yes
Structured PICO
Does finerenone reduce cardiovascular and kidney events and improve CKM syndrome regression in patients with type 2 diabetes and chronic kidney disease across CKM stages?
P
Population
12,990 patients with type 2 diabetes and chronic kidney disease on maximally tolerated renin angiotensin system inhibitor therapy, followed for a median of 3 years.
I
Intervention
Finerenone
C
Comparator
Placebo (both groups on maximally tolerated renin angiotensin system inhibitor therapy)
O
Outcome
Cardiovascular composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and a kidney composite outcome of kidney failure, a sustained 57% or more decrease in eGFR from baseline over 4 weeks or more, or death from kidney failurecomposite
Finerenone reduces cardiovascular and kidney events and promotes CKM syndrome regression across all stages of cardiovascular-kidney-metabolic syndrome in patients with type 2 diabetes and chronic kidney disease.
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The treatment effects were consistent across all clinically relevant subgroups, including those with multiple conditions and those previously treated with an SGLT2 inhibitor or GLP-1 receptor agonist.”
DMDr. Maria A. Pabon
“Importantly, participants who experience new-onset AFib/AFL were at a substantially higher subsequent risk of adverse cardiovascular and kidney outcomes than were those who remained free of AFib/AFL during follow-up. These findings highlight the role of finerenone in reducing the risk of new-onset AFib/AFL, mitigating downstream complications, and ultimately improving outcomes in patients across the CKM spectrum.”
DDDr. Diego Francisco MárquezNephrologist
“These results support a paradigm shift toward earlier intervention in CKM syndrome, with the aim of preserving renal function. Finerenone holds promise for changing the trajectory of CKD within a broader CKM framework. Ongoing trials will further define its role in diverse patient populations and stages of CKM syndrome.”
Implication
Supports finerenone across CKM stages in T2D-CKD; extends prior RCTs to include syndrome regression.
Abstract
Importance: Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has improved outcomes in type 2 diabetes (T2D) and CKD. Objective: To evaluate the efficacy and safety of finerenone across CKM stages, and to examine the effects of finerenone on CKM syndrome progression and regression over time. Design, Setting, and Participants: This study is a post hoc pooled analysis of 2 randomized, double-blind, placebo-controlled, phase 3 multinational, multicenter clinical trials (FIDELITY) and was conducted across 48 countries. Patients with T2D and CKD with estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2 or higher, serum potassium 4.8 mmol/L or less, and taking maximally tolerated renin angiotensin system inhibitor therapy were included and classified into CKM syndrome stages, using American Heart Association criteria. These data were analyzed from September 2025 and March 2026. Intervention: Participants in the pooled trials were randomly assigned to either finerenone or placebo. Main Outcomes and Measures: Cardiovascular composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and a kidney composite outcome of kidney failure, a sustained 57% or more decrease in eGFR from baseline over 4 weeks or more, or death from kidney failure. Results: Among 12 990 participants (mean [SD] age, 64.8 [9.5] years; 3932 women [30%] and 9058 men [70%]) in FIDELITY, 3864 were classified as CKM stage 2 (30%), 3275 stage 3 (25%), and 5851 stage 4 (45%). After a median follow-up of 3 years, stage 4 was associated with a higher incidence of cardiovascular events (adjusted hazard ratio [aHR], 1.87; 95% CI, 1.56-2.24) and kidney events (aHR, 1.96; 95% CI, 1.43-2.69) when compared with stage 2. Finerenone consistently reduced cardiovascular (P for interaction = .86) and kidney (P for interaction = .65) events, irrespective of baseline CKM stage. Absolute rate reductions for the composite cardiovascular outcome were -1.1 per 100 person-years for stage 4 and -0.4 per 100 person-years for stage 2. After 3 years, participants randomized to finerenone were more likely to experience CKM syndrome regression (11.4% vs 7.4%; adjusted odds ratio [aOR], 1.66; 95% CI, 1.30-2.13; P < .001) and less likely to experience CKM syndrome progression (aOR, 0.89; 95% CI, 0.79, 1.00; P = .05) vs placebo. Conclusions and Relevance: Among patients with T2D and CKD in this study, finerenone reduced risks of cardiovascular and kidney events across CKM stages and led to greater CKM syndrome regression, and lesser CKM syndrome progression, over time. Trial Registration: ClinicalTrials.gov Identifier: NCT02540993 and NCT02545049.
Cite This Study
Lo et al. (2026) conducted an RCT in Type 2 diabetes and chronic kidney disease (CKM syndrome) (n=12,990). Finerenone vs. Placebo was evaluated on Cardiovascular composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and a kidney composite outcome of kidney failure, a sustained 57% or more decrease in eGFR from baseline over 4 weeks or more, or death from kidney failure. Finerenone reduced cardiovascular and kidney events across CKM stages and increased CKM syndrome regression (11.4% vs 7.4%; aOR 1.66; 95% CI 1.30-2.13; P<.001) compared with placebo.