Prioritizing Antidiabetic Drugs for Inflammatory Bowel Disease Through Inverse Signal Detection: A FAERS Pharmacovigilance Study

Background/Objectives: Inflammatory bowel disease (IBD) represents a growing therapeutic challenge, and the identification of novel treatment strategies remains an unmet clinical need. Drug repurposing offers a pragmatic and cost-effective alternative to de novo drug development. This study aimed to identify candidate drugs for repurposing in IBD through inverse signal detection within a large spontaneous pharmacovigilance database. Methods: In this observational, retrospective pharmacovigilance study, data from the FDA Adverse Event Reporting System (FAERS) were analyzed using OpenVigil 2.1. Drugs inversely associated with IBD were identified based on a ROR < 1 and an adjusted p-value < 0.05. Candidates were subsequently filtered to exclude agents with implausible indications, unfavorable pharmacokinetic profiles, or recognized contraindications to use in IBD. Although this screening process yielded a broader set of repurposing candidates across multiple drug classes, the present study focused specifically on antidiabetic medications, which were subjected to a targeted literature review evaluating their immunomodulatory properties, anti-inflammatory mechanisms, and existing preclinical and clinical evidence in the context of IBD. Results: Of 3585 initial drug–event combinations evaluated, 73 candidates met predefined criteria for statistical significance, pharmacokinetic feasibility, and clinical relevance. Within this broader pool, ten antidiabetic agents which demonstrated meaningful inverse signal strength were selected for in-depth analysis: dulaglutide (ROR 0.181, 95% CI 0.136–0.242), insulin lispro (ROR 0.206, 95% CI 0.161–0.263), insulin glargine (ROR 0.246, 95% CI 0.205–0.295), insulin (ROR 0.340, 95% CI 0.295–0.390), insulin aspart (ROR 0.349, 95% CI 0.267–0.455), empagliflozin (ROR 0.400, 95% CI 0.311–0.514), liraglutide (ROR 0.419, 95% CI 0.319–0.552), metformin (ROR 0.446, 95% CI 0.407–0.489), sitagliptin (ROR 0.460, 95% CI 0.376–0.563), and semaglutide (ROR 0.622, 95% CI 0.507–0.764). The subsequent literature review discussed relevant immunomodulatory and anti-inflammatory properties for each of these agents, providing a mechanistic rationale for their potential therapeutic role in IBD. Conclusion: This study identifies antidiabetic drugs as plausible repurposing candidates for IBD, supported by both pharmacovigilance-derived inverse signals and a body of mechanistic and clinical literature suggesting shared pathophysiological pathways between the two conditions. However, it should be acknowledged that the clinical evidence supporting the therapeutic efficacy of several candidates remains variable or incomplete, and robust interventional data are largely lacking. Ultimately, the findings of this study generate testable hypotheses and highlight a set of candidate therapies that warrant dedicated experimental and clinical investigation, including well-designed prospective trials, to determine their true therapeutic potential in IBD management.