Dulaglutide, Insulins, Empagliflozin, Liraglutide, Metformin Show Inverse Association with IBD in FAERS

The escalating prevalence of Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, presents a significant and growing therapeutic challenge. Current standard-of-care treatments often involve broad immunosuppressants or biologics targeting specific inflammatory cytokines like TNF-α, but these can have substantial side effects and limited efficacy for many patients. Identifying novel, safer, and more effective treatment strategies remains a critical unmet clinical need. Drug repurposing, leveraging existing medications for new indications, offers a pragmatic and cost-effective pathway to accelerate therapeutic development for complex conditions like IBD.

This observational, retrospective pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) using OpenVigil 2.1. Researchers screened 3585 initial drug-event combinations to identify drugs inversely associated with IBD, defined by a Reporting Odds Ratio (ROR) < 1 and an adjusted p-value < 0.05. Candidate drugs were then filtered based on plausible indications, favorable pharmacokinetic profiles, and absence of contraindications for IBD use. The study specifically focused on antidiabetic medications, subjecting ten selected agents to a targeted literature review to evaluate their known immunomodulatory and anti-inflammatory properties relevant to IBD.

Of the 3585 drug-event combinations initially evaluated, 73 candidates met the predefined statistical, pharmacokinetic, and clinical relevance criteria for an inverse association with IBD. Within this broader pool, ten antidiabetic agents demonstrated particularly meaningful inverse signal strength. The most prominent findings included dulaglutide with an ROR of 0.181 (95% CI 0.136-0.242), followed by insulin lispro (ROR 0.206, 95% CI 0.161-0.263) and insulin glargine (ROR 0.246, 95% CI 0.205-0.295). Other notable antidiabetic drugs showing significant inverse signals were insulin (ROR 0.340), insulin aspart (ROR 0.349), empagliflozin (ROR 0.400, 95% CI 0.311-0.514), and liraglutide (ROR 0.419, 95% CI 0.319-0.552).

Metformin also exhibited a strong inverse association with an ROR of 0.446 (95% CI 0.407-0.489), as did sitagliptin (ROR 0.460, 95% CI 0.376-0.563) and semaglutide (ROR not fully specified in abstract but listed as a top candidate). These inverse signals suggest a lower-than-expected reporting rate of IBD in patients using these antidiabetic medications, hinting at potential protective or therapeutic effects.