Beyond Metabolic Control: Interpreting the Role of GLP-1 Receptor Agonists in Inflammatory Bowel Disease

Authors and AffiliationsMuhammad Hassan Saeed1, Fariha Shahid Tanveer2*1 Jinnah Postgraduate Medical Center, Karachi, Pakistan2 Jinnah Medical and Dental College, Karachi-74800, PakistanCorresponding Author*Farhia Shahid TanveerJinnah Medical and Dental College, Karachi-74800, PakistanEmail: fariha.s.tanveer@gmail.comORCID: 0009-0009-8543-9939Muhammad Hassan Saeed: mhassansaeed124@gmail.comORCID: 0009-0003-6608-6708Word count386To the Editor,We read the systematic review by Maracle et al. regarding GLP-1 receptor agonists (GLP-1RAs) in patients with inflammatory bowel disease (IBD) with great interest.¹ This work is very relevant in context of growing numbers of IBD patients dealing with obesity and metabolic issues. We need to understand how these drugs affect their disease course and long-term health.The potential for GLP-1 signaling to act as an immunomodulator is biologically plausible and clinically significant. Lab studies suggest that receptor activation may help reinforce the intestinal barrier and lower pro-inflammatory cytokines in colitis models.²,³ While we still lack full clinical confirmation, these findings suggest that GLP-1RAs may offer therapeutic benefits beyond weight loss or blood sugar control. Maracle et al.’s findings also align with what we are seeing in real-world data. Observational studies show that starting a GLP-1RA does not appear to increase the risk of flares, steroid use, or IBD-related surgeries—all while providing expected weight loss.⁴,⁵ Other recent meta-analyses support this, showing no higher risk of adverse IBD outcomes compared to patients not taking the drug.⁶ The lack of any link between GLP-1RAs and intestinal obstruction or ileus is a particularly important point in this review.¹ Given that these drugs affect gut motility, this has been a major concern for clinicians. Seeing no association in the registry data is very reassuring for our daily practice.However, we agree with the authors that many uncertainties remain. Most of our current data is observational, making it difficult to prove cause and effect because of potential confounding.¹,⁶ The studies are also very diverse in how they define "IBD activity" and which GLP-1RA was used. This makes it hard to pull the data into a single clear answer. We also noticed a lack of objective measures, like endoscopic scores or biomarkers, in many of these reports.Finally, there is the practical issue of side effects. The nausea and diarrhea caused by GLP-1RAs can look almost exactly like an IBD flare. Without careful monitoring in future trials, it would be easy to mistake a drug side effect for worsening disease.In summary, Maracle et al. have given us a very helpful starting point. We now need prospective trials specifically for IBD patients to help us make better evidence-based decisions in the clinic.References1. Maracle B, Quan S, Hamilton P, et al. Systematic Review: Efficacy, Safety and Metabolic Outcomes of GLP-1 Receptor Agonists in Inflammatory Bowel Disease. Aliment Pharmacol Ther. 2026 Jan;63(1):17-39. doi: 10.1111/apt.70485.2. Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018 Apr 3;27(4):740-756. doi: 10.1016/j.cmet.2018.03.001.3. Colwill M, Povlsen S, Pollok R, et al. Glucagon-like peptide-1 (GLP-1) receptor agonists in inflammatory bowel disease: mechanisms, clinical implications, and therapeutic potential. J Crohns Colitis. 2025 Sep 28;19(9):jjaf167. doi: 10.1093/ecco-jcc/jjaf167. 4. Desai A, Petrov J, Hashash JG, et al. Use of glucagon-like peptide-1 receptor agonists for type 2 diabetes mellitus and outcomes of inflammatory bowel disease. Aliment Pharmacol Ther. 2024 Sep;60(5):620-632. doi: 10.1111/apt.18138.5. Levine I, Sekhri S, Schreiber-Stainthorp W, et al. GLP-1 Receptor Agonists Confer No Increased Rates of IBD Exacerbation Among Patients With IBD. Inflamm Bowel Dis. 2025 Feb 10;31(2):467-475. doi: 10.1093/ibd/izae250.6. Siranart N, Nakaphan P, Pajareya P, et al. Can GLP-1 agonists be used safely in inflammatory bowel disease? A meta-analysis. J Crohns Colitis. 2025 Dec 23;19(12):jjaf193. doi: 10.1093/ecco-jcc/jjaf193.Conflicts of InterestThe author declares no conflicts of interest.FundingNo specific funding was received for this work.Data availabilityNot applicable.AcknowledgementNot Applicable.Ethical approvalThis letter did not involve any patients, so no ethical approval was required.Author ContributionConceptualization (FST, MHS), Literature review (MHS), Writing-Original Draft (MHS), Review and Editing (FST) Supervision (MHS), Correspondence (FST)Author ApprovalAll authors have approved the final version of this letter.