Finerenone Safety Signals Identified in US and Japanese Reports

A dual-database pharmacovigilance study identified known renal and metabolic safety signals for finerenone and flagged four potential new signals among reports involving patients with type 2 diabetes and chronic kidney disease: increased urine albumin-to-creatinine ratio, abnormal hepatic function, penile gangrene and dizziness. Researchers analyzed 1,545 reports in the US Food and Drug Administration’s Adverse Event Reporting System and 210 in the Japanese Adverse Drug Event Report database in which finerenone was listed as the primary suspect drug. The study found that many reports with usable dates described adverse events during the first two months of treatment, but the investigators cautioned that the findings are hypothesis-generating and require prospective validation.

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist approved for the management of chronic kidney disease in patients with type 2 diabetes. Pivotal randomized trials have shown reductions in renal and cardiovascular events, including kidney failure and death, but the authors noted that controlled studies may not capture the full spectrum of rare or long-term adverse events encountered in routine clinical practice. Spontaneous reporting systems offer a complementary view by collecting adverse-event reports after a medicine enters clinical use.

Their coverage is broad, but they do not provide a denominator for exposed patients and cannot determine an event’s incidence or establish that finerenone caused it. Investigators integrated and cleaned seven standardized FAERS tables, standardized missing-value encodings and drug names, and removed duplicate cases according to the FDA’s data-removal guide. Duplicate case records were identified using the primary and case identifiers, with the latest version retained, and corresponding records in the other tables were removed to maintain consistency.

JADER entries were also deduplicated. In both databases, adverse events were coded with Preferred Terms from version 27.1 of the Medical Dictionary for Regulatory Activities, and only reports identifying finerenone as the primary suspect drug were analyzed. Signal detection used the reporting odds ratio, proportional reporting ratio and Medicines and Healthcare products Regulatory Agency comprehensive criteria.

A reporting-odds-ratio signal required at least three reports and a lower bound above one for its 95% confidence interval. A proportional-reporting-ratio signal required at least three reports, a value of at least two and a chi-square value of at least four. Higher reporting odds ratios or proportional reporting ratios indicate stronger disproportionality between a particular drug and event within the reporting database.

The investigators also calculated time to onset by subtracting the reported treatment-start date from the event-onset date, excluding records with missing or erroneous dates, and summarized the intervals with medians. These calculations identify reporting associations and timing patterns rather than causal effects. The reports largely involved men and older adults.

Patients aged 65 to 85 formed the largest specified age group in FAERS, while those aged 70 or older predominated in JADER. The United States submitted 70.94% of the FAERS reports, followed by Japan, China, Israel and Germany, whereas all analyzed JADER reports originated in Japan. Recorded indications centered on chronic kidney disease, type 2 diabetes and diabetic kidney disease.

Report numbers reached their highest level in 2024 in both databases, although this reporting pattern alone does not demonstrate an increase in adverse-event incidence. FAERS yielded 565 Preferred-Term signals involving 2,777 reports across 26 System Organ Classes, while JADER yielded 52 signals involving 242 reports across 18 classes. In both systems, metabolism and nutrition disorders, renal and urinary disorders and various investigations were among the most prominent categories.

Frequently reported terms shared across the databases included hyperkalemia, increased blood potassium, increased blood creatinine, decreased glomerular filtration rate and renal impairment. These terms corresponded with risks already known from finerenone’s clinical evidence and regulatory profile, but their presence in spontaneous reports reflects reporting patterns that can be influenced by underreporting, selection and confounding. After the researchers compared detected events with the known adverse-reaction profile, they classified increased urine albumin-to-creatinine ratio, abnormal hepatic function, penile gangrene and dizziness as potential new signals.

Nausea, diarrhea, hypotension and acute kidney injury also met signal criteria in one or both databases, but the investigators categorized them as secondary or supportive findings because they were less consistent across sources or had already been documented in related clinical trials. A FAERS signal for decreased urine albumin-to-creatinine ratio was not treated as a novel adverse reaction because the decrease is a recognized pharmacodynamic effect of finerenone. In JADER, the terms with the strongest disproportionality included decreased faecal quantity, cardiac catheterization and musculoskeletal disorders, whereas its most common reported terms were hyperkalemia, renal impairment, increased blood potassium, increased blood creatinine and loss of consciousness.

Timing results suggested that a substantial share of dated reports concerned the early treatment period. Among 186 FAERS cases containing the required dates, the median time to onset was 36 days; 84 events, representing 45.16%, occurred during the first month. In JADER, 108 reports contained usable treatment-start and event-onset dates, and the median was 51 days.

Of those JADER reports, 34 events, or 31.48%, occurred in the first month, and 60.18% occurred within the first two months. The authors interpreted these observations as identifying an interval in which monitoring may be especially important. They do not show that adverse events are most likely during that window because the databases lack exposed-patient denominators and depend on clinicians’ and patients’ reporting behavior.

Kidney findings require particular care because finerenone can alter renal hemodynamics soon after initiation, and an early reduction in estimated glomerular filtration rate differs from a sustained decline. Some renal changes may therefore reflect progression of chronic kidney disease rather than a harmful drug effect; concomitant medicines and pre-existing conditions may also contribute. The investigators proposed that dizziness, nausea and diarrhea could be associated with reduced blood pressure or low sodium.

Abnormal hepatic-function results might merit pharmacokinetic study because finerenone is metabolized mainly through CYP3A4, while penile gangrene might involve vascular tone or perfusion in patients with severe pre-existing vascular disease. These proposed mechanisms were not tested in the study and should not be interpreted as demonstrated explanations. The central limitation is the nature of spontaneous reporting.

A report does not establish drug causality, and underreporting and reporting bias are inherent to the systems. Some reports come from consumers and may lack professional accuracy; underlying illnesses and concomitant medications were not fully controlled; and the available data cannot measure how often events occurred among all finerenone users. The authors also noted that disproportionality analyses often generate signals that remain unverified or prove false alarms.

Prospective cohorts, electronic health records and other causal-inference approaches would therefore be needed to determine whether the four candidate signals represent genuine adverse reactions. The paired-database analysis identifies patterns for further study, while its strongest findings remain the recurrence of established renal and metabolic reporting signals and the concentration of dated events early in treatment.

Subject of Research: Pharmacovigilance assessment of finerenone adverse-event reports in patients with type 2 diabetes and chronic kidney disease

Article Title: Real-world safety profile of finerenone in patients with type 2 diabetes and chronic kidney disease: a multi-database pharmacovigilance analysis of the FAERS and JADER systems

Article References: Zhang, D., Zhao, Y., Chen, H., & Miao, Y. (2026). Real-world safety profile of finerenone in patients with type 2 diabetes and chronic kidney disease: a multi-database pharmacovigilance analysis of the FAERS and JADER systems. Frontiers in Clinical Diabetes and Healthcare, 7, Article 1984666. https://doi.org/10.3389/fcdhc.2026.1984666

Image Credits: AI Generated

DOI: 10.3389/fcdhc.2026.1984666

Keywords: finerenone, pharmacovigilance, adverse events, FAERS, JADER, type 2 diabetes, chronic kidney disease, hyperkalemia, renal function, signal detection, drug safety, real-world evidence