Background:
Obesity is prevalent within the inflammatory bowel disease (IBD) population. Several studies suggest that 15%-40% of IBD patients are obese. Obesity has further been associated with higher disease activity and reduced time to flare. With the increase in use of glucagon-like peptide 1 receptor agonist (GLP-1) treatment for obesity, it is important to assess the effectiveness of GLP-1 agonists in weight reduction and the safety of these agents in the IBD patient population. The aim of this study is to determine the safety and clinical effectiveness of GLP-1 agonists for obesity treatment in patients with IBD.

Methods:
We performed a retrospective cohort study in a consecutive series of adult IBD patients seen at University of PA Health system who were prescribed a GLP-1 agonist for at least 3 months between 2017 – 2023. Percent change in weight was calculated after 12-24 weeks of therapy. Patients were excluded if they were treated with steroids, if they did not have a weight recorded between 12-24 weeks after initiation of GLP-1 or if medication was stopped prior to this time. The incidence of adverse events (AEs) while on therapy and discontinuation of therapy was critically evaluated. Multivariable analysis was performed to determine if use of different GLP-1 agonists were independent predictors of significant weight reduction.

Results:
A total of 230 IBD patients using GLP-1 agonists were included; 139 with Crohn’s disease (CD) and 91 with ulcerative colitis (UC). Median age was 58 years and 138 patients (59%) were female. Of the 230 patients started on GLP1 agonist, 25 (11%) experienced AEs – most commonly nausea/vomiting (n=12; 48%) or diarrhea (n=4; 16%). In 23 of 25 patients (92%) who experienced AEs, there was cessation of therapy. There was no cessation of therapy due to IBD flare and furthermore, no life-threatening events reported. GLP-1 agonists led to a significant decrease in weight from 224.7 + 5.05 to 206.8 + 5.15, p=0.02. The mean change in body weight was a 6.7% reduction (SD 13.2). On multivariable regression, after controlling for age, gender, co-morbidities and IBD treatment, there was no significant difference between specific type of GLP-1 agonist and percent change in weight. However, upon stratification into CD and UC, there was a significant association between semaglutide and percent change in weight for CD patients (p=0.03).

Discussion:
Our findings suggest that CD and UC patients can tolerate GLP-1 agonists, with 10% requiring cessation as a consequence of adverse events not related to IBD flares. Furthermore, GLP-1 agonists utilized in patients with IBD lead to a statistically significant decrease in weight. This effect may be stronger in IBD patients (specifically CD patients) prescribed semaglutide. GLP-1 agonists, as a class, should be considered as a useful tool for weight loss in patients with IBD.

Gary Lichtenstein

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