The Safety of Finerenone in Patients with Chronic Kidney Disease during Ramadan Fasting

Abstract

Introduction Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, is used in the management of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and albuminuria. However, the safety of finerenone during Ramadan fasting has not been evaluated previously. This study aims to evaluate the clinical outcomes of finerenone use during Ramadan fasting in this patients group.

Patients and Methods This retrospective cohort study was conducted at Tawam Hospital and Ambulatory Healthcare Services, United Arab Emirates, from July 2023 to July 2024. The study included patients on finerenone therapy and compared them to a control group of patients not using finerenone. Patients were further subdivided into Ramadan fasting and nonfasting groups. Baseline, during Ramadan, and post-Ramadan clinical and laboratory data were analyzed, including glycemic control (hemoglobin A1c [HbA1c]) and renal function (estimated glomerular filtration rate [eGFR]). To assess clinical outcomes and adverse events, descriptive and regression analyses were performed.

Results A total of 42 finerenone-treated patients were compared with 271 controls. Patients in the finerenone group had higher rates of CKD and proteinuria and were on multiple antidiabetic medications. Among patients who observed Ramadan fasting, a decline in eGFR and a decrease in HbA1c were observed in the finerenone group compared with controls. Hypoglycemia was significantly higher in the finerenone group (36.7%) than in the non-finerenone group (13%). Finerenone use and the CKD stage were significant predictors of adverse events.

Conclusion Our study highlights the potential risks associated with finerenone use during Ramadan fasting, including hypoglycemia and renal function decline. These findings emphasize the need for careful patient selection, individualized treatment adjustments, and close monitoring. Larger, prospective studies are needed to validate these observations and provide definitive guidance.

Keywords

finerenone - chronic kidney disease - diabetic kidney disease - T2 diabetes - Ramadan fasting - acute kidney injury - hypoglycemia

Introduction

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has emerged as a significant component for the management of type 2 diabetes mellitus (T2DM) with albuminuria, particularly for patients at risk of cardiovascular complications. Finerenone offers unique therapeutic benefits together with other established therapies, such as renin-angiotensin system (RAS) blockers, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and glucagon-like peptide-1 agonists (GLP-1 A).[1] [2] At this time, there is limited data on the tolerability and safety of finerenone during periods of fasting, such as Ramadan.

Ramadan fasting, observed by most Muslims worldwide, involves abstinence of eating and drinking from dawn to sunset, which presents unique challenges for individuals with chronic conditions like T2DM.[3] [4] This fasting can influence medication adherence, therapeutic effects, and metabolic control, signifying the need for personalized management approach during this period. Finerenone has demonstrated efficacy in reducing the risk of chronic kidney disease (CKD) progression and cardiovascular mortality in landmark trials such as FIDELIO-DKD and FIGARO-DKD.[1] [2] It has been approved for managing diabetic kidney disease (DKD) for patients with an estimated glomerular filtration rate (eGFR) of ≥ 25 mL/min/1.73 m² and the presence of albuminuria, complementing standard care therapies such as RAS blockade and SGLT2i.[5] [6] However, and due to the potential incidence of hyperkalemia and initial deterioration of renal function associated with finerenone use, it is crucial to closely monitor patients, especially during fasting periods.[7]

To date, no clinical studies have investigated the use of finerenone during Ramadan fasting in patients with kidney disease, including those with diabetes, highlighting the need for such research. The primary goal of this study was to evaluate the safety of finerenone use in patients with T2 diabetes and albuminuria, during Ramadan fasting.

Patients and Methods

A retrospective cohort study was conducted at Tawam Hospital and Ambulatory Health Care Services, Al-Ain City, United Arab Emirates, from July 1, 2023, to July 1, 2024. The study adhered to the principles of the Declaration of Helsinki and received approval from the Tawam Hospital Research Ethics Committee [MF2058-2024-1119] and the Ambulatory Healthcare Services Research Ethics Committee [2024-5]. Due to the retrospective nature of this medical chart review, patient consent was not required, and data confidentiality was strictly maintained in compliance with regulatory standards.

All patients with CKD on finerenone before Ramadan were included as a treatment group, and their outcomes were compared with a control group of CKD patients not on finerenone. Both groups were further stratified based on whether they observed fasting during Ramadan. Laboratory data were collected at three time points in the finerenone group: baseline (before Ramadan), during Ramadan, and post-Ramadan (1–3 months after). The control group was CKD patients who were followed in ambulatory health care services and assessed before Ramadan, and their data were available before Ramadan and after Ramadan only. Ramadan fasting occurred from March 11 to April 10, 2024, with an average fasting duration of 15 hours per day. This design facilitated a detailed analysis of the impact of finerenone and fasting on clinical outcomes in CKD patients.

The inclusion criteria included adult patients (≥ 18 years) with an eGFR > 25 mL/min/1.73 m² who had been on finerenone therapy for at least 10 days before the start of Ramadan (March 11, 2024). Patients were excluded if they could not be followed up after Ramadan fasting. Following Ramadan, all patients in both groups (finerenone and non-finerenone) were contacted to gather data on total fasting days, reasons for breaking the fast, complications, and any hospital admissions or emergency department visits. Clinical outcomes were assessed by comparing data related to glycemic control (if applicable), renal function, albuminuria, and other laboratory parameters across fasting and nonfasting patients. The impact of Ramadan fasting on clinical outcomes, including the safety profile of finerenone therapy, was evaluated.

Demographic information, comorbidities, medication history, CKD status, and laboratory data—including renal function markers, lipid panels, hemoglobin A1c (HbA1c) (if applicable), and complete blood counts—were retrieved from electronic medical records. Descriptive statistics were expressed as mean, median with interquartile range, and percentages as appropriate.

Data analysis was performed using the Statistical Package for the Social Sciences (SPSS, version 29, IBM). Statistical significance was defined as p < 0.05. Analytical methods included paired t-tests, logistic regression, and linear regression analyses to assess associations between variables.

Results

A total of 42 diabetic patients on finerenone therapy were compared with 271 diabetic controls not on finerenone. The finerenone group comprised predominantly males (59.5%) compared with 48% in the control group. Local Emirati patients accounted for more than 60% of both groups. Among the finerenone-treated group, 92.9% had T2DM, 97.6% had hypertension (HTN), 95.2% had dyslipidemia, and CKD stages were distributed as 66.7% in stage III and 23.8% in stage II. In contrast, in the non-finerenone group 73% had T2DM, 90.2% had HTN, 75.6% had CKD stage III, and 12.4% had CKD stage II. Proteinuria was notably higher in the finerenone group (38.1%) compared with 8.5% in the non-finerenone group. The baseline mean potassium level for the finerenone group was 4.45 mmol/L. Significant differences were observed in the use of insulin and oral hypoglycemic agents, including SGLT2i, GLP-1A, sitagliptin, and metformin, with the finerenone group more frequently on multiple diabetic medications ([Table 1]).

Table 1 Baseline characteristics between finerenone and non-finerenone groups

	No finerenone	Finerenone	Total	p-Value
Male	130 (48)	25 (59.5)	158 (50.5)	0.164
Female	141 (42)	17 (45.5)	155 (49.5)
Local	165 (60.9)	29 (69)	194 (62)	0.393
No diabetes	71 (26.2)	3 (7.1)	74 (23.6)	0.018
Type 1 diabetes	3 (1.1)	0 (0)	3 (1)
Type 2 diabetes	197(72.7)	39 (92.9)	236 (75.4)
Hypertension	239 (90.2)	41 (97.6)	280 (91.2)	0.147
Statin use	159 (58.7)	40 (95.2)	199 (63.6)	< 0.001
CKD stage
1	6 (2.3)	2 (4.8)	8 (2.6)	< 0.001
2	0 (0)	10 (23.8)	10 (3.2)
3	201 (75.6)	28 (66.7)	22 (74.4)9
4	33 (12.4)	2 (4.8)	35 (11.4)
5	26 (9.8)	0	26 (8.4)
Proteinuria	23 (8.5)	16 (38.1)	39 (12.5)	< 0.001
Insulin	56 (20.7)	15 (35.7)	71 (22.8)	0.046
Sulphonylureas	39 (14.4)	10 (23.8)	49 (15.7)	0.168
GLP-1 RA	4 (1.5)	16 (38.1)	20 (6.4)	< 0.001
SGLT-2 inhibitors	14 (5.2)	32 (76.2)	46 (14.7)	< 0.001
Metformin	14 (5.2)	24 (57.1)	38 (12.1)	< 0.001

Abbreviations: CKD, chronic kidney disease; GLP-1RA, glucagon-like peptide-1 agonists; SGLT-2, sodium-glucose cotransporter 2.

Patients were further divided into Ramadan fasting and nonfasting subgroups. Within the finerenone group, 30 patients fasted and 12 did not; in the non-finerenone group, 240 patients fasted while 31 did not. Baseline characteristics were comparable between fasting and nonfasting groups within each category.

When comparing the finerenone group to the non-finerenone group, significant differences were noted, including a higher mean HbA1c level (7.4%) among fasting patients in the control group versus 6.7% in the fasting finerenone group (p = 0.002). Additionally, the mean eGFR was significantly lower in the fasting finerenone group (43.3 mL/min) compared with the fasting control group (58.6 mL/min, p < 0.001) ([Table 1]). The fasting finerenone group experienced a decline in both eGFR and HbA1c levels during Ramadan. A paired t-test revealed a marginally significant drop in eGFR (4.08 mL/min, p = 0.061) in the fasting finerenone group, but no significant change in the control group ([Table 2]).

Table 2 Determinants of HbA1c after Ramadan (a) and eGFR after Ramadan (b) from studies of risk factors at baseline

a. Determinants of HbA1c after Ramadan
	Beta	p-Value	95% CI for B
HbA1c before	0.511	< 0.001	0.433	0.723
Finerenone	−0.103	0.043	−1.041	−0.017
Insulin	0.028	0.643	−0.364	0.587
Sulphonylureas	0.011	0.831	−0.41	0.509
Age	−0.009	0.866	−0.013	0.011
Diabetes	0.207	< 0.001	0.203	0.661
Sex	0.07	0.173	−0.104	0.575
Cardiac diseases	−0.053	0.322	−0.576	0.19
b. Determinants of eGFR after Ramadan
Finerenone	0.045	0.284	−2.338	7.93
eGFR	0.849	< 0.001	0.835	0.978
Proteinuria	−0.074	0.026	−8.352	−0.549
Age	−0.078	0.013	−0.19	−0.022
GLP1-RA	−0.079	0.034	−13.865	−0.536
Sitagliptin	−0.064	0.064	−13.447	0.377
Fasting	0.005	0.865	−3.115	3.705

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; GLP-1RA, glucagon-like peptide-1 agonists; HbA1c, hemoglobin A1c.

Note: Linear regression with HbA1c after Ramadan as the dependent variable in (a) and eGFR after Ramadan as the dependent variable in (b).

HbA1c levels showed a marginal reduction among fasting finerenone patients (−0.38 mmol/mol, p = 0.063), while the nonfasting finerenone group exhibited a slight increase (0.1 mmol/mol). Similarly, the fasting control group displayed a modest rise (0.22 mmol/mol.), though none of these changes were statistically significant ([Table 2]).

The mean potassium level in the fasting finerenone group remained stable during and after Ramadan (4.46 mmol/L during Ramadan and 4.49 mmol/L 3 months post-Ramadan).

The incidence of significant adverse events among patients using finerenone was higher in the fasting group compared with the nonfasting group (36.7% vs. 16.7%), as was the incidence of hypoglycemia (26.7% vs. 8.3%). Nonhypoglycemic adverse events were slightly lower in fasting patients (10.0% vs. 16.7%) ([Table 3]).

Table 3 Adverse events in finerenone and non-finerenone groups

Fasting status	Finerenone group	Significant adverse events		Hypoglycemia events		Nonhypoglycemic events		Total
		No (%)	Yes (%)	No (%)	Yes (%)	No (%)	Yes (%)
Not fasting	No	30 (73.2)	11 (26.8)	40 (97.6)	1 (2.4)	40 (97.6)	1 (2.4)	41
	Yes	10 (83.3)	2 (16.7)	11 (91.7)	1 (8.3)	10 (83.3)	2 (16.7)	12
Fasting	No	200 (87.0)	30 (13.0)	226 (98.3)	4 (1.7)	217 (94.3)	13 (5.7)	230
	Yes	19 (63.3)	11 (36.7)	22 (73.3)	8 (26.7)	27 (90.0)	3 (10.0)	30
Total	All	259 (82.7)	54 (17.3)	299 (95.5)	14 (4.5)	294 (93.9)	19 (6.1)	313

Linear regression analysis indicated significant associations of hypoglycemia and nonhypoglycemic adverse events ([Table 4]). Finerenone use was significantly associated with a higher risk of hypoglycemia (odds ratio [OR] = 85.3, p < 0.001), even after adjusting for CKD stage, systolic blood pressure, fasting status, and diabetes treatment. However, fasting status itself did not appear to be a significant independent predictor of hypoglycemia in this model. Nonhypoglycemic adverse events were also significantly associated with finerenone use (OR = 4.20, p = 0.044), although other variables, including CKD stage and fasting, were not significant predictors.

Table 4 Logistic regression analysis of the determinants of outcome from the studied risk factors at baseline before Ramadan

a. Hypoglycemia adverse events determinants
	Beta	p-Value	OR	95% CI
Finerenone	4.446	< 0.001	85.3	7.074	1028.849
CKD stage	0.751	0.229	2.12	0.623	7.21
Systolic BP	−0.081	0.015	0.9	0.863	0.984
Age	−0.067	0.08	0.935	0.867	1.008
Hypertension	17.962	0.998	0.78	0
HbA1c before	0.466	0.161	1.6	0.831	3.055
Diabetes	14.267	0.996	5.73	0
Fasting	0.706	0.475	2.03	0.293	14.004
On insulin	1.034	0.278	2.81	0.433	18.266
On sulphonylureas	−1.509	0.232	0.221	0.019	2.621
b. Nonhypoglycemia adverse events determinants
Finerenone	1.434	0.044	4.195	1.038	16.949
CKD stage	0.512	0.223	1.669	0.732	3.807
Systolic BP	0.020	0.217	1.020	0.989	1.052
Age	0.016	0.470	1.016	0.973	1.062
HTN	−1.665	0.095	0.189	0.027	1.338
HbA1c before	−0.076	0.718	0.927	0.614	1.400
Diabetes	0.596	0.295	1.816	0.594	5.549
Fasting	−0.016	0.982	0.984	0.239	4.044
c. Determinants of all adverse events
Finerenone	0.844	0.033	2.326	1.071	5.051
Fasting	−0.206	0.595	0.814	0.381	1.739
On sulphonylureas	−0.739	0.148	0.477	0.175	1.301
Cardiac diseases	0.424	0.202	1.529	0.797	2.934
On insulin	0.719	0.042	2.051	1.027	4.099

Abbreviations: BP, blood pressure; CI, confidence interval; CKD, chronic kidney disease; HbA1c, hemoglobin A1c; HTN, hypertension; OR, odds ratio.

Finerenone use appeared to be a significant predictor of all adverse events combined (OR = 2.33, 95% p = 0.033). Insulin use increased the risk of adverse events independently (OR = 2.05, p = 0.042). Linear regression analysis indicated a significant association between finerenone use and a reduction in HbA1c among fasting patients (B = −0.103, p = 0.043), independent of diabetes medications, age, and sex. Additionally, eGFR after Ramadan was significantly lower among patients on finerenone (B = −0.533, p = 0.049), after adjusting for comorbidities, CKD stage, medication use, and fasting status.

Discussion

This study examined the safety of finerenone and its effects on clinical outcomes in CKD patients, primarily those with T2DM, during Ramadan fasting. Remarkably, patients using finerenone exhibited significant changes in select clinical parameters during fasting, highlighting the need for careful consideration.

As expected, diabetes was significantly more prevalent in the finerenone-treated group compared with the untreated group, reflecting the common use of finerenone for managing DKD.[1] Three nondiabetic patients (7.1%) were on finerenone for nonformulary indications at the time of the study. This small number does not allow for a direct comparison of outcomes between diabetic and nondiabetic patients. Baseline differences between the finerenone and non-finerenone groups were evident, with the former exhibiting higher rates of proteinuria and a broader use of antidiabetic medications, aligning with findings from previous studies.[5] [6] These differences highlight the complexity of managing patients on finerenone during prolonged fasting periods, such as Ramadan. Among fasting finerenone users, a marginally significant decline in both eGFR and HbA1c levels was observed, suggesting potential fasting-related impacts on renal function and glycemic control.[4] [8] [9] [10] The eGFR decline may hold clinical significance, as it indicates a potential effect of finerenone use under fasting conditions, potentially exacerbated by restricted fluid intake and altered metabolic demands during fasting.[1] [2] [5] [6]

The observed reduction in HbA1c among fasting finerenone users with diabetes raises important considerations regarding its potential drivers. These may be finerenone therapy, the physiological effects of fasting, or inadequate adjustments to diabetic regimens during fasting. Notably, this reduction should not be misinterpreted as improved glycemic control, given the associated increased risk of hypoglycemia. The elevated hypoglycemia risk, likely amplified by the combined use of multiple antidiabetic medications and impaired renal clearance, highlights the critical importance of optimizing diabetic management during fasting to prevent adverse outcomes.[11] [12] [13]

Adverse events, particularly hypoglycemic episodes in patients with diabetes, were more common among finerenone users during Ramadan fasting. Advanced CKD stage and finerenone use emerged as significant predictors of such adverse events, underscoring the need for caution and close monitoring of these patients during Ramadan. Individualized adjustments of medication regimens and regular monitoring throughout the fasting may be necessary to mitigate these risks. These findings may also contribute to future clinical guidelines for managing CKD patients during Ramadan fasting,[4] therefore, finerenone may be added to the list of medications requiring careful evaluation during Ramadan fasting, given its potential impact on renal function and glycemic control.

There is a potential risk of developing hyperkalemia in CKD patients who are placed on finerenone treatment, while on the other hand, long fasting increases the risk further in diabetic patients with severe CKD. This phenomenon has been attributed to insulinopenia and a diminished response to epinephrine.[14] Our study showed that the mean potassium level in the fasting finerenone group remained stable during and after Ramadan.

Physicians should utilize the diabetes and Ramadan risk calculator in patients with diabetes[3] or the RAK Initiative Risk Assessment Tool in nondiabetics[4] in order to assess and classify patients' risks. This assessment is critical for guiding patients on whether it is safe to fast and for providing tailored medical advice.

This study has several limitations. This study's retrospective design and small sample size limit the statistical power and generalizability of the findings, making the results exploratory in nature. While robust statistical analyses, including logistic and linear regression models, were employed to adjust for potential confounders such as CKD stage, diabetes status, and medication use, residual confounding factors cannot be entirely ruled out. Additionally, many unmeasured variables such as dietary patterns, fluid intake, fasting practices during Ramadan, and others may have influenced the outcomes and should be considered when interpreting the results.

The higher proportion of nondiabetic patients in the control group (26.2%) compared with the finerenone group (7.1%) likely impacted the observed differences in hypoglycemia rates, as hypoglycemia is more commonly associated with diabetes and the use of many antidiabetic medications. However, with only three nondiabetic patients in the finerenone group, a meaningful comparison between diabetics and nondiabetics within each group was not feasible. Similarly, baseline differences in CKD severity and proteinuria between the finerenone and control groups may have confounded the interpretation of renal function decline during Ramadan fasting. A direct comparison of fasting versus nonfasting finerenone users would have been ideal to isolate the effects of fasting; however, the small sample size of nonfasting individuals limited the statistical power for such analysis.

Medication adherence and fasting practices were self-reported, introducing the potential for recall bias. Additionally, variations in lifestyle factors such as physical activity and dietary adjustments during Ramadan, which were not comprehensively assessed, may have further influenced the outcomes. To address these limitations, future research should focus on larger, prospective, randomized cohorts to better evaluate the effects of finerenone during Ramadan fasting and explore potential strategies for optimizing medication regimens in this unique context.

Conclusion

Our study provides exploratory insights into the safety of finerenone use during Ramadan fasting in patients with CKD and T2DM. While fasting was associated with an increased risk of hypoglycemia and a decline in renal function among finerenone users, these findings must be interpreted cautiously due to the retrospective design, small sample size, and baseline differences between groups. This study is hypothesis-generating and highlights the need for larger, prospective studies to further investigate the observed trends and establish causality.

Careful patient selection, individualized treatment adjustments, and regular monitoring are essential when prescribing finerenone to fasting patients. Additionally, the use of Ramadan risk calculators and comprehensive patient assessments can help guide safe fasting practices and reduce the risk of adverse events.

Conflict of Interest

None declared.

Authors' Contributions

All authors contributed toward conception, data collection, writing, and final approval of the manuscript.

Compliance with Ethical Principles

Ethical approval was obtained from the institutional review board of Tawam Hospital.

• References

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Publication History

Article published online:
01 April 2025