Temporal and Demographic Risks of Ertugliflozin: A Comprehensive FAERS Disproportionality Study Informing Diabetes Management

Abstract Objective This study seeks to quantify varying risks of AEs linked to Ertugliflozin, the latest approved SGLT-2 inhibitor, within age-sex-weight subgroups, and identify crucial risk periods through comprehensive pharmacovigilance analysis utilizing real-world data from the FDA Adverse Event Reporting System (FAERS). Research Design and Methods: This study examined 826 adverse event (AE) reports from the FDA Adverse Event Reporting System (FAERS) covering the period from the first quarter of 2018 to the third quarter of 2025(2018Q1-2025Q3). Four disproportionality algorithms were employed: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network and empirical Bayesian geometric mean (EBGM). Mappings for SOC and PT were consistent with MedDRA version 26.1. Additionally, Weibull distribution modeling and cumulative incidence functions were utilized for temporal risk assessment. Results Among 826 reports, significant safety signals were identified across 10 System Organ Classes. The most notable signals were for urine ketone body present, diabetic ketosis and fungal infection. Stratified analyses revealed distinct risk profiles: females showed higher risks of genital infections, whereas younger adults (18–40 years) exhibited extreme signals for diabetic ketoacidosis. Patients with lower body weight (< 50 kg) had a heightened signal for renal disorders. Notably, no significant signals for cardiac disorders were detected in any subgroup. TTO analysis indicated that 15.25% of AEs with data occurred within 7 days, though TTO was missing in 56.25% of reports. Conclusion Ertugliflozin’s AE profile is characterized by significant associations with ketosis and specific infections, with risk patterns varying meaningfully by demographic factors. These findings underscore the need for vigilant, individualized monitoring, particularly for ketosis in younger patients and genital infections in females. The substantial missing TTO data highlights an area for improved pharmacovigilance reporting.