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Therapeutic Impacts of Oral Anti-Diabetic Drugs on Inflammatory Bowel Disease (Ibd), a Comprehensive Review of Clinical and Preclinical Studies Publisher



Niknejad A ; Hosseini Y ; Nazari Manesh MA ; Navabakhsh M ; Peyrovinasab A ; Mavaddat H ; Miri MS ; Hosseini M ; Busselberg D ; Abdolghaffari AH
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Source: Naunyn-Schmiedeberg's Archives of Pharmacology Published:2025


Abstract

Inflammatory bowel disease (IBD) is a chronic condition with a rising incidence linked to inflammation and oxidative stress. This disorder includes two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). Current treatment plans lack effectiveness; as a result, finding novel approaches is encouraged. Various groups of oral anti-diabetic medications are employed in clinical practice, and they have shown beneficial effects against conditions beyond diabetes mellitus (DM). This review is aimed at evaluating the hypothesis that oral anti-diabetic medications may serve as potential therapeutic agents for IBD due to their anti-inflammatory and antioxidant effects. The current study investigated the protective effects of these agents against IBD. In this review, we gathered evidence from cellular, animal, and clinical studies within the scientific databases Medline, Scopus, and Web of Science regarding the favorable impacts of anti-diabetic drugs on IBD. We explored these databases from their inception to May 2024. Studies focusing on the therapeutic impacts of these medications on diverse models of IBD were included and reviewed. Biguanides, sulfonylureas, thiazolidinediones (TZD), dipeptidyl peptidase 4 inhibitors (DPP4I), and sodium-glucose cotransporter inhibitors (SGLT2I) exhibited protective effects against IBD. These medications promoted gut microbiome balance and the function of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin. Moreover, they affected key cytokines (tumor necrosis factor (TNF), malonaldehyde (MDA)), enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX), myeloperoxidase (MPO)), and signaling pathways (nuclear factor erythroid 2-related factor (Nrf2) transcription factor/hemoxygenase 1 (HO-1), high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor kappa B (NF-κB)). Anti-diabetic medications demonstrated positive effects against IBD. However, further comprehensive clinical assessments are necessary to confirm their efficacy and safety as an adjunctive therapy for IBD. © 2025 Elsevier B.V., All rights reserved.
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