GENDER DIFFERENCES IN THE OCCURRENCE OF NEUROPSYCHIATRIC DISORDERS INDUCED BY DIPEPTIDYL PEPTIDASE-4 INHIBITORS

Abstract Background Neuropsychiatric comorbidities in diabetic patients are becoming an increasingly significant concern. Although gender differences have been identified in the development of neuropsychiatric disorders, the association between gender differences and neuropsychiatric disorders induced by dipeptidyl peptidase- 4 (DPP-4) inhibitors, the most commonly used drugs in the treatment of type 2 diabetes in Japan, has not been fully elucidated. Aims and Objectives In this study, the association between gender differences and neuropsychiatric disorders induced by DPP-4 inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) was explored. Methods In this study, we analyzed 10,676,525 cases registered in the FAERS during the third quarter of FY2021. The targeted neuropsychiatric disorders were defined as psychiatric disorders within the System Organ Class of the Medical Dictionary for Regulatory Activities. To assess the association between gender differences and neuropsychiatric disorders caused by DPP-4 inhibitors, signal scores were used (the frequentist statistical index: relative reporting odds ratio; rROR, and the Bayesian statistical index: information component delta; ICΔ) in the disproportionality analysis. We applied previously reported signal detection criteria, which included having a minimum of 3 reports, a lower limit of the 95 % confidence interval for rROR (rROR025) >1, and a lower limit of the 95 % credible interval for ICΔ (ICΔ 025) >0. Results Two signals associated with males were detected. In contrast, nine signals linked to females, including confusion (rROR025: 1.16, ICΔ025: 0.24), aphasia (rROR025: 1.93, ICΔ025: 1.09), and personality disorder (rROR025: 8.34, ICΔ025: 3.74), were identified. Discussion and Conclusion This study elucidated gender differences in DPP-4 inhibitor-induced neuropsychiatric disorders through pharmacoepidemiological analysis based on the FAERS. Notably, gender differences were identified in DPP-4 inhibitor-induced neuropsychiatric disorders, particularly warranting special attention in females. Consequently, it is crucial to assess the mental status of female patients with diabetes during treatment with a DPP-4 inhibitor.