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Review
. 2025 Jul 15:16:1610368.
doi: 10.3389/fimmu.2025.1610368. eCollection 2025.

GLP-1 receptor agonists in IBD: exploring the crossroads of metabolism and inflammation

Giulia Migliorisi  1   2 , Roberto Gabbiadini  1 , Arianna Dal Buono  1 , Matteo Ferraris  1   2 , Giuseppe Privitera  1   2 , Lorenzo Petronio  1   2 , Peter Bertoli  1   2 , Cristina Bezzio  1   2 , Alessandro Armuzzi  1   2
Affiliations
Review

GLP-1 receptor agonists in IBD: exploring the crossroads of metabolism and inflammation

Giulia Migliorisi et al. Front Immunol. .

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represent a cornerstone in the treatment of diabetes and obesity and have emerged as a promising option for other metabolic disorders, including hepatic steatosis. Recent evidence highlights the direct and indirect anti-inflammatory properties of GLP-1, suggesting a potential additional therapeutic strategy for patients with inflammatory bowel disease (IBD). However, side effects of GLP-1 RAs, particularly those affecting the gastrointestinal system, may limit their use in patients with IBD. The rising prevalence of IBD worldwide and the ageing of the IBD population will likely increase the number of patients with metabolic comorbidities who may potentially benefit from a combination treatment with GLP-1 RAs. A profound comprehension of the physiological function of intestinal homeostasis and permeability is essential to more accurately evaluate the prospective application of GLP-1 RAs in patients with ongoing inflammation. While preclinical studies support this hypothesis, robust clinical evidence remains limited. This narrative review aims to provide a synthesis of current knowledge regarding the anti-inflammatory properties of GLP-1, with a particular focus on safety concerns and potential future directions for its use in IBD management.

Keywords: GLP-1; GLP-1 receptor agonists; IBD; diabetes; obesity.

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Conflict of interest statement

Author AA has received consulting fees from AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz and Takeda; speaker’s fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Tigenix; and research support from Biogen, MSD, Takeda, and Pfizer. Author CB received lecture fees and served as a consultant for Takeda, MSD, Ferring, Abbvie, Galapagos and Janssen. R. Author RB has received speaker’s fees from Pfizer, MSD, Celltrion and Takeda. Author AB has received speaker’s fees from AbbVie, Galapagos, Celltrion and Pfizer. G. Author GP has received speaker’s fees from Janssen and Alphasigma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The image in panel (A) illustrates how various metabolites derived from diet and gut microbiota (bile acids, tryptophan, LPS, SCFAs) stimulate enteroendocrine L-cells in the intestinal mucosa to secrete GLP-1. GLP-1 acts both locally at the level of the intestinal epithelium and systemically through blood vessels and immune cells. GLP-1 reduces IFN-γ, crypt cell apoptosis, and cytotoxicity by intraepithelial lymphocytes (IELs) and at the same time, it stimulates the proliferation of intestinal epithelial cells (IECs) and L-cells, as well as mucin production by Brunner’s glands (37, 41, 49, 50, 61). Moreover, GLP-1 RAs are found to be associated with alteration of intestinal microbiota (11, 72). Panel B is a concise representation of the role of GLP-1 in immune responses. GLP-1 modulates monocytes/macrophages, promoting polarization toward M2 macrophages (anti-inflammatory), which release IL-10 and suppress pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Furthermore, it Influences indirectly T helper lymphocytes polarisation to Th2 cells and release of IL-5 and IL-10, contributing to a more tolerogenic immune response (41, 44). Overall, GLP-1 acts as an immuno-metabolic modulator, supporting intestinal barrier protection and a regulated inflammatory response.
See this image and copyright information in PMC

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