Sexual Safety Signals of Common Antidiabetic Drugs: Insights From FAERS Disproportionality Analysis.

BACKGROUND: Erectile dysfunction is a prevalent and distressing complication of diabetes mellitus that markedly affects quality of life in male patients. Although the role of diabetes in erectile dysfunction is well-established, potential drug-induced sexual dysfunction associated with commonly prescribed antidiabetic medications remains underrecognized. The objective of this study was to investigate whether commonly prescribed antidiabetic medications, including glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, metformin, and sodium-glucose cotransporter-2 inhibitors, are associated with an increased reporting of erectile dysfunction in real-world clinical practice. METHODS: This retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System. A disproportionality analysis was performed to evaluate the reporting frequency of erectile dysfunction associated with commonly prescribed antidiabetic medications. The reporting odds ratio served as the primary metric for evaluating disproportionality in adverse event reporting. In addition, time-to-onset and Weibull shape parameter analyses were performed to assess temporal trends in adverse event occurrence. RESULTS: We identified 49 semaglutide-, 54 sitagliptin-, and 42 dapagliflozin-associated erectile dysfunction reports. All three drugs demonstrated significant disproportionality signals: semaglutide (reporting odds ratio: 1.53, 95% confidence interval: 1.16-2.03; information component = 0.19), sitagliptin (reporting odds ratio: 1.52, 95% confidence interval: 1.16-1.98; information component = 0.20), and dapagliflozin (reporting odds ratio: 1.51, 95% confidence interval: 1.11-2.04; information component = 0.13). Time-to-onset analysis indicated a random failure-type distribution for all three drugs (semaglutide, sitagliptin, and dapagliflozin), suggesting that the occurrence of erectile dysfunction appears relatively random over the course of treatment rather than concentrated shortly after initiation and underscoring the need for continuous monitoring throughout therapy. Other agents in the same drug classes, including dulaglutide, linagliptin, and metformin, did not show significant signals. CONCLUSIONS: This FDA Adverse Event Reporting System-based pharmacovigilance analysis identified potential safety signals linking erectile dysfunction to semaglutide, sitagliptin, and dapagliflozin. These findings do not establish causality and should be regarded as preliminary and hypothesis-generating. Further mechanistic and prospective clinical studies are needed to determine whether these signals reflect true drug-related risks. Clinicians should be aware that erectile dysfunction has been reported in some users of these agents and may consider incorporating sexual health into routine discussions and shared decision-making with male patients.