The Role of GLP-1 Receptor Agonists in IBD-related Surgery and IBDrelated Complications of Inflammatory Bowel Disease Among Patients With Metabolic Comorbidities: A Systematic review and Meta-analysis

Mengqi Yang¹Yujia Huo^2,3,4Zhining Liu⁵Guannan Bai⁶Dongjun He^7*Lin Zhang^2,3,8*

• ¹Monash University, Melbourne, Australia
• ²The School of Public Health and Preventive MedicineDepartment of Epidemiology and Preventive Medicine, The School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
• ³The School of Public Health and Preventive Medicine, Suzhou, China
• ⁴Suzhou Industrial Park Monash Research Institute of Science and Technology, Monash University, Suzhou, China
• ⁵Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
• ⁶Department of Child Health Care, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
• ⁷Department of Endocrinology, The Second People's Hospital of Quzhou, Quzhou, China
• ⁸Southeast University-Monash University Joint Graduate School, Suzhou, China

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes and obesity, and emerging evidence suggests potential immunomodulatory effects. However, few studies have evaluated their role in inflammatory bowel disease (IBD), and no comprehensive clinical trials exist. This meta-analysis aimed to assess the association between GLP-1RA use and IBDrelated surgeries and complications.Methods: A systematic literature search was conducted in PubMed, Embase, and Web of Science from inception to March 2025. Cohort studies comparing IBD patients treated with GLP-1RAs versus nonusers were included. Two reviewers independently performed study selection and data extraction. Random-effects meta-analyses were performed using log-transformed effect sizes. Heterogeneity was assessed using I² and τ². Publication bias was evaluated through funnel plots, and certainty of evidence was graded using the GRADE framework.Results: Six studies were included, providing eight effect estimates (two studies contributed two cohorts each). Three of the six included studies (50%) were non-peer-reviewed conference abstracts, which may affect interpretability. For IBD-related surgery (4 effect estimates), GLP-1RA use was significantly associated with lower risk (pooled estimate: 0.45; 95% CI: 0.35-0.59; I² = 38.1%). For IBD-related complications (4 estimates), GLP-1RA use showed a non-significant trend toward benefit (estimate: 0.39; 95% CI: 0.15-1.03), with high heterogeneity (I² = 98.9%). Sensitivity analysis supported robustness for surgery but revealed instability in complication outcomes. Funnel plots showed no publication bias for surgery, but asymmetry was noted for complications.Conclusions: GLP-1RA use may reduce the risk of IBD-related surgery among IBD patients with metabolic comorbidities. Findings for IBD-related complications should be interpreted with caution due to substantial heterogeneity and the inclusion of abstract-only studies. Further prospective research is warranted.