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17 December 2025 | Volume 20, Issue 4

GLP-1 receptor agonists (GLP-1 RAs) and IBD: the intersection between metabolism and gut inflammation

Written by
Richard Pollok

EpiCom Member

The rising pandemic of obesity has led to the increasing use of GLP-1 receptor agonists (GLP-1 RAs). Their impact on Inflammatory Bowel Disease (IBD) has become a topic of interest as a result and has been the subject of a recent comprehensive review published in J Crohns Colitis [1]. GLP-1 RAs have been reported to have possible effects on IBD, but are improved outcomes related to weight loss or a direct effect of these agents? GLP-1 RAs were originally developed for type 2 diabetes and obesity. Mechanistic work demonstrated that GLP-1 signalling can also modulate intestinal epithelial integrity, mucosal immune responses and the microbiome in pre-clinical colitis models, providing a biologically plausible rationale for a role beyond weight reduction [2].

Mechanisms

In  summary, pre-clinical studies of anti-inflammatory signalling and findings from and observational studies of clinical datasets suggest GLP-1 RAs may confer dual metabolic and disease-modifying advantages in IBD, particularly in people with obesity, but evidence from prospective trials is lacking [2].  Preclinical studies, in animal models of colitis, suggest that GLP-1-based therapies may attenuate gut inflammation. Proposed mechanisms include inhibition of pro-inflammatory signalling (NF-κB, MAPK), preservation of epithelial barrier integrity, modulation of gut microbiota and immunomodulation of both mucosal and systemic inflammation.

Observational studies

Intriguingly, a large population-based study found that the prevalence of de novo IBD among obese patients exposed to weight loss medications, including GLP-1 RAs, was roughly half that among patients with persistent obesity who had not been exposed to these agents [3]. A recent meta-analysis pooled available observational cohorts and registry studies to evaluate IBD clinical outcomes (hospitalisation, surgery, steroid use, escalation to advanced therapies) [4]. The authors reported signals of improved composite outcomes in patients receiving GLP-1 RAs, especially among obese subgroups, but there was significant heterogeneity among studies, potential confounding by indication and reliance on retrospective designs. As an example of the complexity in interpreting these data, GLP-1 RAs also appear to have a role in managing bile salt malabsorption, which is relatively common in IBD [5].

Some observational studies have reported no increase in IBD exacerbations after GLP-1 RA initiation [6] and others have found treatment with GLP-1 RAs to be associated with reduced IBD-related hospitalisation and surgery [7]; however, case ascertainment, concurrent therapies and short follow-up limit causal inference. Safety signals most commonly relate to gastrointestinal adverse effects (nausea, vomiting, change of bowel habit), with GLP-1 RA-related gastrointestinal side effects occurring in around a tenth of individuals. Furthermore, there have been rare reports of pancreatitis. Such side effects require careful monitoring in clinical practice [1].

Clinical implications and research priorities

When considering the use of GLP-1 RAs in patients with IBD and comorbid obesity or diabetes, practising clinicians need to recognise the need for shared decision-making that weighs metabolic benefits against limited prospective efficacy data and evolving safety data. It is necessary to monitor disease activity closely, to document baseline endoscopic/biomarker status where possible and to ensure coordination between the IBD and metabolic teams.

Research priorities now, include adequately powered randomised controlled trials (stratified by obesity status), mechanistic studies linking mucosal GLP-1 signalling to clinical endpoints and longer-term safety surveillance. Such trials are already ongoing, an example being COMMIT-UC: “Mirikizumab Administered at the Same Time as Tirzepatide in Adult Participants With Moderately to Severely Active Ulcerative Colitis and Obesity or Overweight: Phase 3b Study” (NCT06937086). If randomised controlled trials confirm disease-modifying effects, GLP-1 RA could reshape multidisciplinary management for an important subset of patients with IBD.

Selected references (key recent papers)

  1. Knoedler S, Schliermann R, Knoedler L, et al. Impact of sarcopenia on outcomes in surgical patients: a systematic review and meta-analysis. Int J Surg 2023;109:4238–62.
  2. Seminerio JL, Koutroubakis IE, Ramos-Rivers C, et al. Impact of obesity on the management and clinical course of patients with inflammatory bowel disease. Inflamm Bowel Dis 2015;21:2857–63.
  3. Massironi S, Viganò C, Palermo A, et al. Inflammation and malnutrition in inflammatory bowel disease. Lancet Gastroenterol Hepatol 2023;8:579–90.
  4. Ryan E, McNicholas D, Creavin B, Kelly ME, Walsh T, Beddy D. Sarcopenia and inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 2019;25:67–73.
  5. Gold SL, Raman M, Sands BE, Ungaro R, Sabino J. Review article: Putting some muscle into sarcopenia-the pathogenesis, assessment and clinical impact of muscle loss in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2023;57:1216–30.
  6. Skrzypczak D, Ratajczak AE, Szymczak-Tomczak A, Dobrowolska A, Eder P, Krela-Kaźmierczak I. A vicious cycle of osteosarcopenia in inflammatory bowel diseases – aetiology, clinical implications and therapeutic perspectives. Nutrients 2021;13:293.
  7. Fitzpatrick JA, Melton SL, Yao CK, Gibson PR, Halmos EP. Dietary management of adults with IBD – the emerging role of dietary therapy. Nat Rev Gastroenterol Hepatol 2022;19:652–69.
  8. Borba VZC, Costa T. Sarcopenic obesity: a review. Arch Endocrinol Metab 2025;68:e240084.
  9. Scaldaferri F, Pizzoferrato M, Lopetuso LR, et al. Nutrition and IBD: Malnutrition and/or sarcopenia? A practical guide. Gastroenterol Res Pract 2017;2017:8646495.
  10. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing 2019;48:16–31.
  11. Fu H, Wang L, Zhang W, Lu J, Yang M. Diagnostic test accuracy of ultrasound for sarcopenia diagnosis: A systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2023;14:57–70.
  12. Kokura Y, Nishioka S, Maeda K, Wakabayashi H. Ultrasound utilized by registered dietitians for body composition measurement, nutritional assessment, and nutritional management. Clin Nutr ESPEN 2023;57:173–80.
  13. Bischoff SC, Bager P, Escher J, et al. ESPEN guideline on clinical nutrition in inflammatory bowel disease. Clin Nutr 2023;42:352–79.
  14. Eckert KG, Abbasi-Neureither I, Köppel M, Huber G. Structured physical activity interventions as a complementary therapy for patients with inflammatory bowel disease – a scoping review and practical implications. BMC Gastroenterology 2019;19:115.
  15. Donnelly M, Driever D, Ryan ÉJ, et al. Obesity, sarcopenia and myosteatosis: Impact on clinical outcomes in the operative management of Crohn's Disease. Inflamm Bowel Dis 2024;30:1517–28.
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