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Effect of Injectable Dual and Single Agonist Glucagon-Like Peptide-1 Based Therapy on Inflammatory Bowel Disease Activity Among Patients with Obesity

Levine, J.; Lee, Y. A.; Pham, A.; Guo, J.; Dai, H.; Radwan, R.; Bian, J.; Novikov, A.; Sheer, A.

2025-11-15 gastroenterology
10.1101/2025.11.13.25340005 medRxiv
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Background and AimsObesity is a risk factor for relapsing inflammatory bowel disease. GLP-1 and dual GLP-1/GIP agonists may offer superior weight loss; however, their effect on inflammatory bowel disease remains unknown. In this study, we assessed outcomes in patients with IBD and obesity using these medications. MethodsA retrospective, propensity-matched analysis was conducted using data from The OneFlorida+ network. We evaluated patients with IBD and obesity prescribed GLP-1-based therapy (liraglutide, semaglutide, or tirzepatide) versus those without. 562 patients prescribed GLP-1-based therapies were matched 1:1 to controls based on demographics and comorbidities. ResultsNo differences in GLP-1 users versus non-users with respect to all-cause hospitalization, IBD-hospitalization, IBD-related surgery, or pancreatitis were seen. Use of semaglutide reduced the risk of IBD-related surgery (HR 0.33, CI 0.13-0.83). Among 89 tirzepatide users, none required IBD-related surgery versus 2 matched controls. Black GLP-1 users had an increased risk of all-cause hospitalizations (HR 1.59, CI 1.11-2.29) but not IBD-related hospitalization or IBD-related surgery. Steroid use was comparable between groups. GLP-1 use significantly reduced serum CRP. ConclusionsSemaglutide appeared to lower the risk of IBD-related surgery. Black patients using GLP-1 therapy had an increased risk of all-cause hospitalization. Tirzepatide showed no significant difference regarding primary endpoints; however, the sample size was small. Overall, all GLP-1-based therapies were well tolerated among obese patients with IBD. Larger studies are warranted to understand the therapeutic potential of GLP-1-based treatment in this patient population. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/25340005v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1641f43org.highwire.dtl.DTLVardef@40979borg.highwire.dtl.DTLVardef@a16e60org.highwire.dtl.DTLVardef@559e7f_HPS_FORMAT_FIGEXP M_FIG C_FIG

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