Comparative efficacy and safety of finerenone in diabetic kidney disease: a meta-analysis of Asian and non-Asian populations

Abstract

Background & objective

Diabetic kidney disease (DKD) is a major global burden, especially in Asia. This study aimed to evaluate the efficacy and safety of finerenone in diabetic kidney disease, comparing outcomes between Asian and non-Asian populations through a systematic review and meta-analysis.

Methods

A systematic search was conducted across PubMed, Cochrane Library, ClinicalTrials.gov, Google Scholar, and the Undermind AI platform from inception through March 2025. Studies included randomized controlled trials (RCTs) and subgroup analyses that evaluated finerenone in DKD patients. Primary outcomes included a reduction in the urinary albumin-to-creatinine ratio (UACR) and a decline in the estimated glomerular filtration rate (eGFR) of ≥40%. Secondary outcomes included cardiovascular events, mortality due to kidney failure, hyperkalemia (serum potassium >5.0 mmol/L), treatment discontinuation, hospitalization, and adverse event–related mortality. Risk ratios (RRs) and mean differences (MDs) were pooled using a random-effects model, and subgroup analyses were performed by ethnicity.

Results

Five eligible studies, comprising 8,763 participants, were included in this analysis. Finerenone significantly reduced UACR compared with placebo (MD = −0.38, 95% CI −0.42 to −0.35; p < 0.001), with consistent effects across Asian and non-Asian populations (subgroup p = 0.28). It also significantly reduced the risk of eGFR decline ≥40% (MD = −0.24 [−0.40, −0.09]; p = 0.002), with a greater benefit in the Asian subgroup (subgroup p = 0.03). Cardiovascular event risk was also reduced (RR = 0.85 [0.77–0.95]; p = 0.004), while mortality due to kidney failure showed a non-significant reduction (RR = 0.83 [0.64–1.07]; p = 0.15). Hyperkalemia risk was higher with finerenone (RR = 1.73, 95% CI 1.39–2.14), whereas adverse event–related mortality was lower (RR = 0.65, 95% CI 0.46–0.91).

Conclusion

Finerenone provides robust renoprotective and cardioprotective effects in DKD, with broadly consistent efficacy across Asian and non-Asian populations. A greater renal benefit was observed in Asians for eGFR decline ≥40%, though this requires cautious interpretation. Hyperkalemia risk was increased but largely manageable. These findings support integration into DKD therapy and highlight the need for ethnically inclusive, long-term, real-world trials.

Clinical trial number

Not applicable.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12882-025-04526-0.

Introduction

Chronic kidney disease (CKD) is one of the most severe and prevalent complications of type 2 diabetes mellitus (T2DM), commonly referred to as diabetic kidney disease (DKD). Globally, approximately 30–40% of individuals with T2DM develop CKD during their lifetime [1], positioning diabetes as the leading cause of end-stage renal disease (ESRD) in many parts of the world [2, 3]. The burden of DKD is not merely clinical—it is socio-economic and public health–relevant. Between 1990 and 2017, the incidence of DKD rose by an alarming 74%, contributing significantly to global morbidity, mortality, and healthcare costs [4]. Asia has emerged as a focal point of this growing crisis. With the highest share of the global diabetes population—led by China and India—Asia bears the heaviest burden of diabetes-related CKD [1]. For instance, nearly 31% of individuals with diabetes in China present with CKD, while Japan reports a DKD prevalence of approximately 25% to 27% among diabetic patients [5, 6]. India, projected to exceed 130 million diabetes cases by 2045, faces a looming wave of kidney complications [1]. Furthermore, Asian populations often develop CKD at younger ages and lower body weights than their Western counterparts, thereby compounding the clinical and economic burden of DKD in this region [4].

Traditionally, DKD management has emphasized glycemic control and blood pressure management, with renin–angiotensin–aldosterone system (RAAS) blockade using ACE inhibitors or angiotensin receptor blockers (ARBs) as the standard of care. These agents reduce intraglomerular pressure and proteinuria, but their ability to halt CKD progression is limited [7]. Intensification of RAAS blockade has been unsuccessful due to adverse events, particularly hyperkalemia and acute kidney injury [8]. Other interventions, such as dietary protein restriction and lipid-lowering therapy, have yielded modest or inconsistent results [9]. The advent of sodium–glucose cotransporter-2 (SGLT2) inhibitors has brought meaningful progress. These agents reduce albuminuria and slow GFR decline while also reducing cardiovascular risk [10]. Still, many patients continue to experience progressive kidney function loss, indicating a persistent unmet need for additional therapies. Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist (MRA), offers a novel mechanism of reno-cardiovascular protection. Unlike steroidal MRAs, such as spironolactone, finerenone exhibits higher selectivity for the mineralocorticoid receptor and reduced hormonal side effects [11]. It inhibits aldosterone-induced pro-inflammatory and pro-fibrotic pathways, thereby reducing structural damage to both the kidneys and the cardiovascular system [12, 13]. The pivotal FIDELIO-DKD and FIGARO-DKD trials demonstrated finerenone’s efficacy in reducing the risk of kidney disease progression and cardiovascular events in patients with T2DM and CKD already receiving optimized RAAS blockade [14–16]. These findings represent the first time an MRA has demonstrated definitive benefits in both renal and cardiovascular outcomes in this population. Subsequent pooled analyses, including the FIDELITY meta-analysis, have confirmed that these benefits extend across different stages of CKD [17].

The Kidney Disease: Improving Global Outcomes [18] guidelines now recommend finerenone as an adjunctive therapy in T2DM patients with CKD and albuminuria. This represents a paradigm shift in DKD management, expanding beyond RAAS inhibitors and SGLT2i to include finerenone as a foundational therapy for cardiorenal protection. Despite these advancements, questions remain regarding finerenone’s efficacy and safety across ethnically diverse populations, particularly among Asians. Historically, Asian patients have been underrepresented in global trials. While the FIDELIO-DKD and FIGARO-DKD trials included participants from Asia, the sample size was relatively small, and dedicated subgroup analyses are limited. These populations may present unique challenges, such as higher baseline albuminuria, distinct dietary habits (e.g., higher potassium intake), and greater predisposition to hyperkalemia [19]. Emerging post hoc analyses have attempted to address these gaps. For example, a subgroup analysis of Asian participants from FIDELIO-DKD revealed consistent renoprotective benefits, but a slightly higher rate of hyperkalemia, particularly among those with a baseline serum potassium level of ≥ 4.8 mmol/L [20, 21]. These findings suggest that while the efficacy of finerenone remains robust, safety profiles may require closer monitoring in specific ethnic groups. The implications of these findings extend beyond clinical efficacy. Given Asia’s disproportionate burden of T2DM and DKD, and the potential for ethnic variability in drug response and tolerability, region-specific data are critical for personalized medicine. To date, few studies have focused exclusively on South Asian populations, including those from India and Pakistan, nations with a rapidly rising diabetes burden and high rates of progression to ESRD. Addressing this gap is essential to developing equitable and effective therapeutic strategies.

Considering this, the present meta-analysis aims to comprehensively evaluate the efficacy and safety of finerenone in patients with diabetic CKD, with particular focus on differences between Asian and non-Asian populations. By synthesizing data from randomized controlled trials and subgroup analyses, this study seeks to determine whether finerenone’s therapeutic profile is consistent across diverse populations or if adjustments in risk management are necessary. Moreover, the study emphasizes clinically relevant outcomes, such as the urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), incidence of cardiovascular events, mortality due to renal failure, and safety outcomes, including hyperkalemia and adverse events leading to treatment discontinuation. The findings will contribute to a more nuanced understanding of how best to incorporate finerenone into the therapeutic landscape for diabetic CKD—particularly in underrepresented regions like South Asia. By contextualizing finerenone within the broader evolution of DKD management, and by identifying key regional considerations in its clinical use, this analysis aims to guide clinicians, researchers, and policymakers toward a more equitable, effective, and data-driven approach to treating diabetic kidney disease globally.

Methodology

Study objectives

This meta-analysis aimed to comprehensively evaluate the efficacy and safety of finerenone in managing chronic kidney disease (CKD) in patients with type 2 diabetes, with a specific focus on comparisons between Asian and non-Asian populations. The primary objectives were: To assess the effectiveness of finerenone in reducing UACR, an important biomarker of renal function; To evaluate the impact of finerenone on reducing the progression of CKD by assessing eGFR decline; To determine the incidence and severity of hyperkalemia and other adverse events associated with finerenone treatment.

Search strategy

We conducted a comprehensive literature search in PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar up to March 2025. In addition, we screened the Undermind AI tool, an artificial intelligence–assisted literature mining platform, to ensure no eligible studies were missed; however, only peer-reviewed articles from standard databases were included in the final analysis. Medical Subject Headings (MeSH) and keywords used in the search included terms such as “finerenone,” “mineralocorticoid receptor antagonists,” “chronic kidney disease with type 2 diabetes,” and “diabetic kidney disease.” We also reviewed references from included articles and performed forward citation searching to identify additional eligible studies. The complete search strategy is provided in Supplementary File S1. This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [22].

Eligibility criteria

Studies were included if they met the following criteria: [1] enrolled adult patients diagnosed with DKD; [2] evaluated the effects of finerenone administered alongside standard care (e.g., renin–angiotensin system inhibitors); [3] included a comparator group receiving placebo with standard care; [4] reported at least one relevant clinical outcome, including UACR, eGFR, cardiovascular events, or safety endpoints such as hyperkalemia, treatment discontinuation, or adverse event–related mortality; and [5] were randomized controlled trials (RCTs) or post hoc subgroup analyses of RCTs published in peer-reviewed journals. For analysis, participants were broadly categorized as Asian or non-Asian. The non-Asian group encompassed White, Black, and Hispanic participants, acknowledging inherent heterogeneity. Exclusion criteria comprised: studies involving non-diabetic kidney disease populations; interventions not involving finerenone; non-interventional study designs (e.g., reviews, editorials, case reports, conference abstracts, animal or in vitro studies); and studies lacking sufficient outcome data. Articles not published in English were also excluded.

Study screening and selection

All retrieved records were imported into Rayyan AI software. After removing duplicates, two reviewers (A.H. and F.Q.) independently screened the titles and abstracts, and disagreements were resolved through discussion or by a third reviewer (U.Y.). The full texts of potentially eligible articles were assessed against the inclusion and exclusion criteria. We included five studies—comprising randomized controlled trials and subgroup analyses—that reported separate data for Asian and non-Asian subgroups. These included broader Asian and non-Asian cohorts [19], China [20], Japan [21], Black population [23], and Hispanic population [24].

Data extraction and quality assessment

Two reviewers (M.M. and S.A.R.) independently extracted relevant data using a standardized extraction form. Extracted data included study characteristics (e.g., author, year, country, sample size, design), intervention and comparator details, and outcome measures. The primary outcome was UACR reduction. Secondary outcomes included eGFR decline, cardiovascular outcomes, hyperkalemia incidence, treatment discontinuation, hospitalization, and death. For dichotomous outcomes, event counts and the total number of participants were extracted. For continuous outcomes, mean values, standard deviations, and sample sizes were recorded. Risk of bias was independently assessed by two reviewers (M.M. and S.A.R.) using the Cochrane Risk of Bias 2.0 tool for RCTs. The following domains were evaluated: randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of reported results. Each domain was graded as low, high, or some concerns, and disagreements were resolved by discussion or with a third reviewer.

Statistical analysis

We used Review Manager (RevMan) version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark) for all statistical analyses. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled for dichotomous and continuous outcomes, respectively, using the Mantel–Haenszel method with a random-effects model, given the expected clinical and methodological heterogeneity. Subgroup analyses compared Asian versus non-Asian populations and explored heterogeneity across chronic kidney disease stages and study populations. Statistical heterogeneity was assessed using Cochran’s Q (p < 0.10) and quantified with I². Publication bias for each meta-analytic outcome was assessed visually using funnel plots, which are provided in Supplementary File (SF1).

Results

The systematic search identified 683 records. After removing duplicates and screening for eligibility, five randomized controlled trials and subgroup analyses were included, comprising 8,763 patients with diabetic kidney disease. These represented six distinct subgroups: one each from Japan, China, and a broader Asian cohort, and three from non-Asian populations (Black, Hispanic, and other global regions). The intervention arm (finerenone plus standard care) included 4,423 patients, while the control arm (placebo plus standard care) included 4,340 patients. Median participant age ranged from 60 to 66 years, with follow-up durations between 3 and 34 months. Study characteristics are summarized in Table 1, and the selection process is shown in Fig. 1. Risk of bias assessment (ROB 2.0) indicated some concerns in three studies, primarily related to missing outcome data and selective reporting (Fig. 2).

Table 1.

Summary of included studies evaluating the efficacy and safety of finerenone in DKD patients among Asian and non-Asian populations

Primary author and year of study	Population		Study design	Enrolled	Age ± SD years	Total participants (Male/ Female)	Finerenone group	Placebo group	Intervention	Control	Follow-up time (Months)
Katayama et al., 2017 [21]	Asian Population Data	CKD and Type 2 Diabetes: Asian (Japanese Group)	ARTS-DN Japan was a multicenter phase 2b RCT study.	96	62.9 ± 10.1	77/19	84	12	Finerenone 1.25-20 mg/day; Oral	Placebo*	3
Zhang et al., 2023 [20]		CKD and Type 2 Diabetes: Asian (Chinese Group)	The FIDELIO-DKD Subgroup from China	372	60.3 ± 10.1	290/82	188	184	Finerenone 10–20 mg/day; Oral	Placebo*	30
Koya et al., 2023 [19]		CKD and Type 2 Diabetes: Asian	A FIDELIO-DKD post hoc Analysis	1,327	63 ± 10	980/347	665	662	Finerenone 15.9 mg/day; Oral	Placebo*	32.4
Koya et al., 2023 [19]	Non-Asian Population Data	CKD and Type 2 Diabetes: non-Asian (ROW Group)	A FIDELIO-DKD post hoc Analysis	4,347	66 ± 9	3003/1344	2168	2179	Finerenone 14.9 mg/day; Oral	Placebo*	31.2
Rosas et al., 2023 [24]		CKD and Type 2 Diabetes: non-Asian (Hispanic Group)	Post hoc analysis of the FIDELITY prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD RCTs.	2,099	64.2 ± 9.7	1292/807	1065	1034	Finerenone 16.5–17.4 mg/day; Oral	Placebo*	31.2
Flack et al., 2023 [23]		CKD and Type 2 Diabetes: non-Asian (Black American Group)	A Post hoc Analysis of the Pooled FIDELIO-DKD and FIGARO-DKD Trials	522	61.8 ± 10.0	284/ 238	253	269	Finerenone 10–20 mg/day; Oral	Placebo*	33.6

*Angiotensin-converting enzyme inhibitors, Angiotensin receptor blockers, Beta-blockers, Diuretics (including Loop and Thiazide diuretics), Statins, Potassium supplements, and Potassium-lowering agents. Glucose-lowering therapies included Insulin and its analogs, Metformin, Sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors

Note: The table summarizes key characteristics of the included randomized controlled trials and post hoc subgroup analyses, including study design, population, sample size, intervention details, and follow-up duration

Fig. 1.

PRISMA flow diagram of study selection. Flowchart depicting the study selection process, including records identified, screened, excluded, and studies included in the meta-analysis comparing Asian and non-Asian DKD populations

Fig. 2.

Risk of bias assessment using ROB 2.0 Tool. (a) Traffic light plot illustrating risk of bias judgments across key domains for each included RCT; (b) Summary plot presenting overall risk of bias judgments across all studies and domains. Domains assessed included randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selective reporting

Publication bias was assessed using funnel plots for each meta-analytic outcome. Visual inspection revealed no major asymmetry, suggesting a low risk of publication bias. The corresponding funnel plots are provided in Supplementary File 1 (Figs. 3B, 4, 5, 6, 7, 8, 9 and 10B), alongside their respective forest plots (Figs. 3, 4, 5, 6, 7, 8 and 9 A).

Fig. 3.

Forest plot for UACR reduction with finerenone. Forest plot of pooled risk ratios for UACR reduction, including subgroup analysis by ethnicity

Fig. 4.

Forest plot for eGFR decline ≥ 40%. Finerenone effect on ≥ 40% decline in eGFR, with subgroup comparison between Asian and non-Asian populations

Fig. 5.

Forest plot for incidence of mortality due to kidney failure. Risk ratios for death due to kidney failure, comparing finerenone with placebo across all studies and ethnic subgroups

Fig. 6.

Forest plot for cardiovascular event reduction. Summary of cardiovascular outcome data showing risk reduction with finerenone. The forest plot includes subgroup analysis by ethnicity and the overall pooled effect (RR with 95% CI)

Fig. 7.

Forest plot for overall hyperkalemia risk. Comparison of hyperkalemia incidence in finerenone-treated versus placebo-treated groups. The forest plot includes subgroup analysis (Asian vs. non-Asian) and pooled RR estimates

Fig. 8.

Forest plots for moderate and severe hyperkalemia. (a) Risk of moderate hyperkalemia (serum potassium > 5.5 mmol/L) with finerenone versus placebo. (b) Risk of severe hyperkalemia (serum potassium > 6.0 mmol/L). Both outcomes include pooled RRs with subgroup comparisons

Fig. 9.

Forest plots for hyperkalemia-related discontinuation and hospitalization. (a) Incidence of treatment discontinuation due to hyperkalemia; (b) Incidence of hospitalization related to hyperkalemia. Forest plots include pooled RRs and subgroup analysis

Fig. 10.

Forest plot for adverse events leading to death. Comparison of adverse event–related mortality between finerenone and placebo groups. Forest plot displays pooled RR and 95% CI, showing a significantly lower risk in the finerenone group

Efficacy outcomes

UACR: Finerenone significantly reduced the UACR compared with placebo, indicating improved renal outcomes in DKD patients. The pooled mean difference was − 0.38 [95% CI: −0.42 to − 0.35]; p < 0.001, with no heterogeneity detected (I² = 0%). Subgroup analyses showed consistent benefits in both Asian (MD = − 0.36 [− 0.41 to − 0.31]) and non-Asian populations (MD = − 0.40 [− 0.45 to − 0.35]). The test for subgroup differences was not statistically significant (p = 0.28; I² = 15.2%), indicating that the UACR-lowering effect of finerenone is consistent across Asian and non-Asian populations (Fig. 3A), with the corresponding funnel plot provided in Fig. 3B (SF1). In addition, eGFR Decline ≥ 40%: Finerenone also significantly reduced the risk of eGFR decline ≥ 40% compared to placebo, with a pooled mean difference of − 0.24 [95% CI: −0.40 to − 0.09]; p = 0.002. Subgroup analyses demonstrated a stronger protective effect in Asian patients (MD = − 0.40 [− 0.59 to − 0.20]; p < 0.001) compared to non-Asian patients (MD = − 0.13 [− 0.26 to − 0.01]; p = 0.04). The subgroup difference reached statistical significance (p = 0.03), suggesting that Asian populations may derive greater renal benefits from finerenone therapy (Fig. 4A), with the corresponding funnel plot shown in Fig. 4B (SF1).

Mortality and Cardiovascular Outcomes: Finerenone showed a non-significant trend toward reduced mortality due to kidney failure compared with placebo (RR = 0.83 [95% CI: 0.64–1.07]; p = 0.15) (Fig. 5A). Importantly, heterogeneity across studies was absent (I² = 0%), and the test for subgroup interaction was not significant (p = 0.75), indicating consistency of findings across Asian and non-Asian populations. The corresponding funnel plot is provided in Fig. 5B (SF1). For cardiovascular outcomes, finerenone significantly reduced the overall risk of cardiovascular events (RR = 0.85 [95% CI: 0.77–0.95]; p = 0.004) (Fig. 6A). Subgroup analyses showed no significant effect in Asian patients (RR = 0.84 [95% CI: 0.62–1.13]; p = 0.25) but a significant risk reduction in non-Asian patients (RR = 0.86 [95% CI: 0.76–0.96]; p = 0.008). Heterogeneity was absent both overall and within subgroups (I² = 0%), and the test for subgroup differences was not significant (p = 0.91), suggesting that the cardiovascular protective effect of finerenone is broadly consistent across ethnic populations. The corresponding funnel plot is shown in Fig. 6B (SF1).

Safety outcomes

Safety analyses highlighted an increased risk of hyperkalemia and related adverse outcomes, but severe events were infrequent and generally manageable.

Overall Hyperkalemia: Finerenone significantly increased the risk of hyperkalemia compared with placebo (RR = 1.73 [95% CI: 1.39–2.14]; p < 0.001). Subgroup analyses showed elevated risk in both Asians (RR = 1.53 [1.25–1.86]; I² = 0%) and non-Asians (RR = 2.11 [1.28–3.48]; I² = 67%), with no statistically significant subgroup difference (p = 0.24). Although non-Asian populations exhibited numerically higher relative risks of hyperkalemia compared to Asian populations, formal tests for subgroup differences did not reach statistical significance, suggesting that ethnicity may not be a strong independent modifier of risk. Overall heterogeneity was moderate (I² = 40%). Sensitivity analyses, conducted by sequentially excluding individual studies, confirmed the robustness of this association, as the direction and magnitude of effect remained unchanged (Fig. 7A; funnel plot, Fig. 7B, SF1).

Moderate and Severe Hyperkalemia: Finerenone more than doubled the risk of moderate hyperkalemia (> 5.5 mmol/L) (RR = 2.20 [1.97–2.46]; p < 0.001; I² = 0%), with consistent effects across subgroups (Fig. 8a; funnel plot, Fig. 8A, SF1). Severe hyperkalemia (> 6.0 mmol/L) risk was nearly tripled (RR = 3.00 [2.25–4.00]; p < 0.001), also without heterogeneity (I² = 0%) (Fig. 8b; funnel plot, Fig. 8B, SF1).

Hyperkalemia-Related Treatment Discontinuation and Hospitalization: The incidence of treatment discontinuation due to hyperkalemia was significantly higher among patients receiving finerenone, with a pooled RR of 2.61 [1.77 to 3.85] (p < 0.001). This risk was consistent across both Asian and non-Asian subgroups (I² = 0%, subgroup p = 0.66) (Fig. 9a), with the corresponding funnel plot shown in Fig. 9A (SF1). Similarly, the risk of hospitalization due to hyperkalemia was significantly elevated in the finerenone group (RR = 3.30 [1.49 to 7.29], p = 0.003), although the overall event rates remained low. There was minimal heterogeneity (I² = 8%), and no evidence of subgroup effect (Fig. 9b), with the corresponding funnel plot shown in Fig. 9B (SF1).null

Adverse events leading to death: Finerenone significantly reduced the risk of adverse event–related mortality (RR = 0.65 [95% CI: 0.46–0.91]; p = 0.01). Importantly, heterogeneity across studies was absent (I² = 0%), and the test for subgroup interaction was not significant (p = 0.46), indicating consistency of this protective effect across Asian and non-Asian populations (Fig. 10A; funnel plot, Fig. 10B, SF1).

Discussion

This meta-analysis provides a comprehensive evaluation of the efficacy and safety of finerenone in patients with DKD, with a particular emphasis on comparisons between Asian and non-Asian populations. The findings reinforce finerenone’s role as a dual-action therapy that significantly improves renal and cardiovascular outcomes in a broad spectrum of DKD patients, while also highlighting the importance of vigilant monitoring due to the elevated risk of hyperkalemia.

Our pooled analysis demonstrated that finerenone significantly reduces UACR, with a pooled mean difference was − 0.38 (p < 0.001), confirming its antiproteinuric effects. This reduction aligns with prior findings from the FIDELIO-DKD and FIGARO-DKD trials, which reported a ~ 30–40% decrease in UACR from baseline [14, 25]. UACR is a strong surrogate marker for disease progression and cardiovascular risk [21], and our meta-analysis further validates the clinical relevance of UACR reduction with finerenone. Finerenone also significantly attenuated the decline in eGFR, with a pooled mean difference of − 0.24 (95% CI: − 0.40 to − 0.09). This result is consistent with the observed preservation of eGFR in prior clinical trials. The overall renal benefit in our analysis was further supported by reductions in composite endpoints, including kidney failure, sustained decline in eGFR, and renal death. Although the reduction in mortality due to kidney failure did not reach statistical significance in our analysis (RR = 0.83), the trend favored finerenone, in agreement with the FIDELITY pooled analysis [17].

Cardiovascular benefits were also evident in our meta-analysis, with finerenone reducing the incidence of cardiovascular events by 15% (RR = 0.85). These findings align with earlier clinical trial data, which show 13–14% reductions in cardiovascular morbidity with finerenone [23, 25]. These results are particularly important for DKD patients, who are at elevated cardiovascular risk. In terms of safety, our pooled data confirmed that finerenone was associated with an increased risk of hyperkalemia (RR = 1.85), particularly at serum potassium levels >5.5 mmol/L and >6.0 mmol/L. However, severe hyperkalemia events remained rare, and the overall incidence of adverse event–related deaths was significantly lower in the finerenone group (RR = 0.65). These safety findings are consistent with those reported in large-scale trials and affirm that, with appropriate patient selection and monitoring, the benefits of finerenone outweigh the risks. This underscores the importance of individualized therapy and rigorous electrolyte monitoring protocols.

Subgroup analyses by ethnicity

Subgroup analyses in our meta-analysis aimed to determine whether finerenone’s efficacy and safety differed meaningfully between Asian and non-Asian populations. Overall, the trends were consistent across ethnicities, with some statistically significant variations in effect magnitude for specific outcomes. UACR: Finerenone demonstrated a robust antiproteinuric effect across both ethnic groups, with no significant subgroup difference (p = 0.28). Our pooled mean difference for UACR reduction was − 0.38 (95% CI: −0.42 to − 0.35), aligning with prior findings, such as the ~ 32% UACR reduction in Hispanic patients [24] and the ~ 40% reduction reported in Black patients [23], affirming the consistency of finerenone’s antiproteinuric effect across ethnicities. Similarly, eGFR Decline ≥ 40% showed a statistically significant subgroup difference (p = 0.03), with the Asian population experiencing a greater protective effect (mean difference = − 0.40 [95% CI: − 0.59, − 0.20]) compared to the non-Asian population (–0.13 [95% CI: − 0.26, − 0.01]). These results support prior subgroup analyses, including the FIDELIO-DKD post hoc analysis by Koya et al.’s study [19], which reported a 30% reduction in renal outcomes in Asians (HR 0.70), compared to ~ 12% in non-Asians (HR 0.88). The significant difference in eGFR decline between Asian and non-Asian patients (p = 0.03) may partly reflect baseline imbalances, such as proteinuria burden, RAAS inhibitor dosing, or dietary potassium intake. Although proteinuria was consistently reported, data on potassium intake and RAAS inhibitor dosing were not uniformly available, limiting our ability to fully adjust for these factors. Biological mechanisms, including pharmacogenomic variation (e.g., CYP450 or mineralocorticoid receptor polymorphisms), heightened aldosterone sensitivity, and differences in sodium handling, may also contribute to the stronger renal benefit observed in Asian subgroups. Future meta-analyses with individual patient-level data, including sensitivity analyses excluding baseline imbalances, will be required to confirm the robustness of this finding.

However, kidney disease-related mortality outcome did not reach statistical significance in either subgroup, though the direction of effect consistently favored finerenone (RR < 1). Our results (no heterogeneity, I² = 0%; subgroup p = 0.75) were in line with the FIDELITY meta-analysis findings that reported similar trends. Additionally, our analysis revealed a significant reduction in cardiovascular events among non-Asians (RR = 0.86, p = 0.008), whereas the result in Asians was not statistically significant (RR = 0.84, p = 0.25). Despite this, the subgroup difference was not significant (p = 0.91), indicating an overall consistent effect across populations. These findings align with those from FIDELIO and FIGARO-DKD, which reported HRs of 0.87–0.88 across different regions [25]. Although our findings support the renoprotective and cardioprotective effects of finerenone, the relatively short follow-up durations (median 2.5–3 years) in the included trials limit conclusions about long-term outcomes such as progression to ESRD and all-cause mortality. Future studies with extended follow-up and real-world data will be essential to confirm whether the observed benefits translate into durable reductions in kidney failure and survival.

Finerenone was associated with an increased risk of hyperkalemia in both groups, with a slightly higher risk in non-Asians (RR = 2.11) compared to Asians (RR = 1.53). The subgroup difference approached but did not reach statistical significance (p = 0.24). Risks of moderate and severe hyperkalemia, as well as hyperkalemia-related treatment discontinuation and hospitalization, were consistent across subgroups (p >0.05 for all). These findings are in line with prior literature reporting no disproportionate risk across ethnicities [20, 23]. Although non-Asian populations exhibited numerically higher relative risks, the lack of statistical interaction suggests ethnicity is unlikely to be a strong independent modifier of risk. This apparent difference may instead reflect unmeasured factors such as baseline dietary potassium intake, variations in background RAAS inhibitor use, or differences in trial-specific discontinuation thresholds. Importantly, severe hyperkalemia events were uncommon and generally manageable across all populations.These results confirm that finerenone offers broad therapeutic value across diverse populations. The enhanced renal benefit observed in Asian populations warrants further investigation into potential contributing factors, including pharmacogenomics and clinical baseline characteristics. Continued efforts are necessary to ensure the inclusion of underrepresented populations, particularly South Asians, to extend the applicability of finerenone’s benefits globally.

Limitations

This meta-analysis has several important limitations. First, most included studies were subgroup or post hoc analyses of the pivotal FIDELIO-DKD and FIGARO-DKD trials, which may increase the risk of reporting bias and limit the strength of conclusions. Second, baseline imbalances between populations—such as proteinuria burden, RAAS inhibitor dosing, or dietary potassium intake—may have influenced the observed subgroup differences in eGFR decline. We extracted and summarized available baseline characteristics (body weight, BMI, baseline eGFR, diabetes duration, HbA1c) stratified by ethnicity; however, data were incomplete or inconsistently reported across trials. As a result, a formal meta-regression was not feasible, and future meta-analyses using individual patient-level data (IPD) will be necessary to clarify whether these baseline factors account for observed ethnic differences. Third, classifying participants as “Asian” versus “non-Asian” obscures the considerable heterogeneity within these broad categories. In particular, South Asians (India, Pakistan, Bangladesh) remain underrepresented despite carrying a disproportionately high burden of DKD, and dedicated prospective trials in these populations are urgently needed. Fourth, potential biological mechanisms for the stronger renal benefit in Asians—such as pharmacogenomic variation (e.g., CYP450 or MR gene polymorphisms), differences in aldosterone sensitivity, or sodium handling—remain speculative, as mechanistic data were not available from the included trials. Fifth, the apparently higher hyperkalemia risk observed in non-Asians may reflect unmeasured confounders including dietary potassium intake, concomitant therapies, or trial-specific thresholds for drug discontinuation. Sixth, follow-up durations in the included studies were relatively short (median 2.5–3 years), limiting assessment of long-term outcomes such as progression to ESRD and all-cause mortality. Seventh, most included studies were conducted before widespread uptake of SGLT2 inhibitors, which restricts the applicability of our findings to current “triple therapy” regimens combining RAAS blockade, SGLT2 inhibitors, and MRAs. Finally, while funnel plots suggested low risk of publication bias, the small number of included studies limits the reliability of these assessments.

An important contextual consideration is that the included trials were conducted before widespread adoption of SGLT2 inhibitors. As current KDIGO and American Diabetes Association (ADA) guidelines increasingly recommend combination therapy, finerenone should be considered within the broader ‘triple therapy’ paradigm of RAAS blockade, SGLT2 inhibition, and mineralocorticoid receptor antagonism. While mechanistic synergy is plausible—given complementary effects on intraglomerular hemodynamics, inflammation, and fibrosis—real-world evidence and prospective trials are needed to clarify the safety and additive efficacy of these regimens across diverse patient populations [10].

Clinical relevance and future directions

Our findings reinforce finerenone as an effective therapy for DKD, offering consistent renoprotective (albuminuria reduction, slower eGFR decline) and cardioprotective (fewer cardiovascular events) benefits across Asian and non-Asian populations. Importantly, the renal benefit appeared more pronounced in Asians, though this may be partly explained by baseline differences such as proteinuria burden or concomitant RAAS inhibitor dosing. Hyperkalemia risk was increased in both groups but remained generally manageable under careful monitoring, with severe outcomes rare. These results align with KDIGO guideline recommendations and support the use of finerenone as part of routine DKD management [18]. However, critical evidence gaps remain. Long-term effects on ESRD progression and all-cause mortality are uncertain given the relatively short trial durations. The role of finerenone in patients with advanced CKD (eGFR < 25), those intolerant of ACEi/ARBs, or those from high-risk but underrepresented groups such as South Asians requires further study. As SGLT2 inhibitors are now standard of care, the integration of finerenone into “triple therapy” regimens (RAAS blockade + SGLT2i + MRA) warrants urgent real-world evaluation. Future trials should also explore mechanistic explanations (e.g., pharmacogenomics, sodium handling, dietary potassium) and use IPD to investigate whether baseline factors drive observed ethnic differences. Expanding inclusion of South Asian populations is especially critical to address the global DKD burden.

Conclusion

This meta-analysis demonstrates that finerenone provides clinically meaningful renoprotective and cardioprotective effects in patients with DKD. Subgroup analyses showed broadly consistent efficacy across Asian and non-Asian populations, with a statistically significant greater renal benefit in Asians for the outcome of eGFR decline ≥ 40%. For albuminuria reduction and cardiovascular outcomes, the effects were directionally similar across ethnicities, with no significant subgroup interaction. Hyperkalemia risk was increased in both populations, with numerically higher relative risks in non-Asians; however, subgroup tests did not reach statistical significance, and severe adverse outcomes remained infrequent and manageable.

These findings support the role of finerenone across diverse patient populations. However, the observed ethnic differences should be interpreted cautiously, given incomplete baseline data, relatively short follow-up, and reliance on post hoc subgroup analyses. Future ethnically inclusive trials, particularly in South Asian populations, are needed to confirm these findings, clarify potential pharmacogenomic and dietary mechanisms, and assess long-term outcomes, including ESRD and mortality, within contemporary “triple therapy” regimens (RAAS blockade, SGLT2 inhibitors, MRAs).

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

S.A.R. and M.M. conceptualized the study, performed data extraction and quality assessment, and drafted the manuscript. A.H. and F.Q. independently screened titles and abstracts; U.Y. resolved discrepancies and contributed to study selection. A.S., F.F., and A.M. assisted in data interpretation and literature contextualization. A.H.A., A.Sajid, S.I., and A.Mohsin critically reviewed the clinical relevance of the findings from an internal medicine perspective. S.T.S., B.M., R.S., and F.F. provided cardiology input on cardiovascular outcome interpretation. Z.N., A.Mand, and P.L. contributed nephrology expertise and reviewed renal endpoint analysis. A.Shaikh, A.R., and A.Rizwan provided endocrinology oversight and reviewed metabolic and safety outcomes. J.A. and S.Abbasi contributed to clinical methodology design and final approval. U.S. and A.Q. assisted with manuscript structure and reference management. All authors reviewed and approved the final manuscript. Corresponding authors: Syed Abbas Raza < sabbasraza@hotmail.com>, Azizul Hasan Aamir < profahaamir@gmail.com>, Syed Tahir Shah < drtshah80@gmail.com>, and Javed Akram <javed.akram@rcp.ac.uk.

Funding

This study received financial support from Nabiqasim Industries (Private) Limited to support research activities. Metrics Research Private Limited contributed in-kind support for data analysis, interpretation, and manuscript preparation. The authors declare no conflicts of interest related to this work.

Data availability

The datasets used and/or analysed during the current study were extracted from publicly available sources. Extracted summary data and synthesis tables are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable. This meta-analysis was conducted using only previously published data and did not involve direct interaction with human participants. Therefore, ethics approval from an institutional review board (IRB) or ethics committee was not required.

Consent for publication

Not applicable. This study did not include any individual patient data or identifiable images. All data were obtained from published, de-identified sources.

Competing interests

The authors declare no competing interests.