In a matched study of 1,124 obese IBD patients, semaglutide reduced the risk of IBD-related surgery by 67% (HR 0.33) and all GLP-1-based therapies significantly reduced CRP inflammation marker levels.
HR 0.33Semaglutide users had a 67% lower risk of IBD-related surgery compared to matched controls, in a propensity-matched study of obese IBD patients
What the researchers found
Semaglutide use was associated with a 67% reduction in IBD-related surgery risk (HR 0.33, 95% CI 0.13-0.83). Among 89 tirzepatide users, none required IBD-related surgery (versus 2 matched controls), though the sample size was too small for statistical significance. GLP-1 use significantly reduced serum C-reactive protein (CRP), suggesting anti-inflammatory effects. No differences were found in all-cause hospitalization, IBD-hospitalization, or pancreatitis rates between GLP-1 users and non-users overall.
Notably, Black GLP-1 users had increased all-cause hospitalization risk (HR 1.59, CI 1.11-2.29) but not IBD-specific hospitalization or surgery, suggesting factors beyond IBD may be driving this disparity.
Why it matters
Obesity worsens IBD outcomes, and many IBD patients are obese. This is among the first studies to examine whether GLP-1 receptor agonists — already taken by many obese patients — could have secondary benefits for IBD management. The finding that semaglutide reduced surgery risk by 67% suggests these peptide drugs may have clinically meaningful anti-inflammatory effects relevant to autoimmune gut conditions.
How the study worked
Retrospective propensity-matched cohort study using the OneFlorida+ clinical data network. 562 patients with IBD and obesity who were prescribed GLP-1-based therapy (liraglutide, semaglutide, or tirzepatide) were matched 1:1 to controls based on demographics and comorbidities. Outcomes assessed included all-cause hospitalization, IBD-related hospitalization, IBD-related surgery, pancreatitis, steroid use, and serum CRP levels.
What this study cannot tell us
This is a retrospective observational study (preprint, not yet peer-reviewed), which cannot establish causation. The tirzepatide group was small (n=89), limiting conclusions about this drug specifically. The propensity matching may not account for all confounders. The racial disparity in hospitalization risk needs further investigation. As a preprint on medRxiv, the findings have not undergone formal peer review.
How to read the evidence
This is a retrospective propensity-matched cohort study published as a preprint (not yet peer-reviewed). While the matched design and meaningful sample size (1,124 patients) provide useful real-world evidence, the retrospective nature and lack of randomization limit causal conclusions. The preprint status means findings should be interpreted with additional caution.
When this study was published
Published as a preprint in 2025, this is very recent research addressing an emerging clinical question. It has not yet undergone peer review.
The bigger picture
This study adds to growing evidence that GLP-1 receptor agonists have anti-inflammatory properties beyond their metabolic effects. The reduction in IBD-related surgery and CRP levels aligns with preclinical data showing GLP-1R signaling modulates immune responses and intestinal inflammation. If confirmed in larger studies, this could position GLP-1 agonists as dual-purpose therapies for obese patients with autoimmune conditions.
Questions still open
- What mechanism explains semaglutide's apparent protective effect against IBD-related surgery — is it weight loss, direct anti-inflammatory action, or both?
- Why did Black patients on GLP-1 therapy show increased all-cause hospitalization risk, and is this related to the medications or to other factors?
- Would prospective clinical trials of semaglutide in IBD patients (regardless of obesity) show therapeutic benefit for the underlying disease?
Common questions
Could semaglutide become a treatment for inflammatory bowel disease?
Are GLP-1 receptor agonists safe for people with IBD?
Read the original research
Effect of Injectable Dual and Single Agonist Glucagon-Like Peptide-1 Based Therapy on Inflammatory Bowel Disease Activity Among Patients with Obesity.
medRxiv : the preprint server for health sciences
Citation
Levine, Jake; Lee, Yao An; Pham, Angela; Guo, Jingchuan; Dai, Hao; Radwan, Rotana M; Bian, Jiang; Novikov, Aleksey; Sheer, Amy. (2025). Effect of Injectable Dual and Single Agonist Glucagon-Like Peptide-1 Based Therapy on Inflammatory Bowel Disease Activity Among Patients with Obesity.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.11.13.25340005