Association of gynecomastia with antidiabetic medications in older adults: data mining from different national pharmacovigilance databases.

OBJECTIVE Gynecomastia is a benign proliferation of the glandular breast tissue in men and is generally caused by a decrease in androgen and an increase in estrogen. Diabetes has been reported to be a risk factor for lowering androgen levels. Moreover, lowered androgen levels are more common in older men. In the present study, we aimed to evaluate the signals for gynecomastia in older men on antidiabetic medications. MATERIALS AND METHODS A disproportionality analysis was performed to detect the signals for antidiabetic drug-associated gynecomastia in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER), using the reporting odds ratio (ROR) and information component (IC). RESULTS Among 8 classes of medications for diabetes, a signal was detected only for dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR: 1.90, 95% confidence interval (CI): 1.27 - 2.83; IC: 0.84, 95% CI: 0.26 - 1.42) in the FAERS. Regarding individual drugs, ROR and IC signals were detected for sitagliptin (ROR: 2.37, 95% CI: 1.48 - 3.79; IC: 1.12, 95% CI: 0.44 - 1.79) and vildagliptin (ROR: 3.34, 95% CI: 1.39 - 8.08; IC: 1.26, 95% CI: 0.07 - 2.44) in the FAERS and only for sitagliptin (ROR: 4.84, 95% CI: 1.92 - 12.2; IC: 1.48, 95% CI: 0.24 - 2.73) in the JADER. CONCLUSION This study showed an association between DPP-4 inhibitor use and gynecomastia in older men with diabetes. Further pharmacoepidemiological studies are warranted to verify this finding.