Comparison of IBD-related outcomes in patients with obesity treated with GLP-1 receptor agonists versus bariatric...

The global prevalence of obesity is rising, paralleled by an increase in IBD (inflammatory bowel disease). While studies examining the impact of obesity on IBD have yielded conflicting results, some suggest that obesity may increase adverse outcomes, whereas BS (bariatric surgery) has been associated with improved IBD outcomes in patients with obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a less invasive alternative to BS for managing obesity, with recent studies indicating potential benefits for IBD outcomes. However, GLP-1 RAs have not been directly compared with BS in patients with obesity and IBD.

We conducted a retrospective cohort analysis using TriNetX, a database aggregating data from over 200 healthcare organizations across the United States. Adult patients with IBD were identified using ICD-10 codes. The cohort was divided into two groups: patients with obesity and IBD prescribed GLP-1 RAs (dulaglutide, semaglutide, liraglutide, lixisenatide, exenatide, albiglutide, or tirzepatide) who had not undergone BS, and patients with obesity and IBD who underwent BS but had not received GLP-1 RAs. To ensure active exposure, GLP-1 RA use required at least two prescriptions separated by at least 1 month. Propensity score matching was performed based on demographics, comorbidities, and IBD medications. Categorical variables were compared using chi-square tests, and continuous variables were compared using independent t-tests. Effect estimates were reported as odds ratios (ORs) with 95% confidence intervals (CIs), with statistical significance defined as P < .05.

A total of 17142 patients with obesity and IBD were identified, including 12965 patients treated with GLP-1 RAs and 4177 patients who underwent BS. Patients in the GLP-1 RA group were older at index (56.7 vs 52.9 years). They also had higher rates of comorbidities, including diabetes (64.3% vs 31.5%), chronic kidney disease (19.6% vs 14.1%), and nicotine dependence (20.4% vs 19.1%), but lower rates of alcohol use disorder (2.3% vs 4.6%), compared with the BS group. The GLP-1 RA group also had higher baseline use of IBD-related medications, including corticosteroids, immunomodulators, and biologic therapies. After propensity score matching, 3478 patients were included in each cohort. Despite a higher post-intervention BMI (body mass index) (34.5 vs 33.4 kg/m²; P < .0001) and shorter follow-up, patients treated with GLP-1 RAs demonstrated significantly lower odds of lower extremity deep venous thrombosis (OR 0.24, 95% CI, 0.16-0.35), pulmonary embolism (OR 0.27, 95% CI, 0.17-0.41), Clostridioides difficile infection (OR 0.22, 95% CI, 0.14-0.34), intestinal obstruction (OR 0.21, 95% CI, 0.15-0.29), abdominal pain (OR 0.34, 95% CI, 0.28-0.42), nausea (OR 0.42, 95% CI, 0.35-0.50), constipation (OR 0.44, 95% CI, 0.37-0.53), colectomy (OR 0.13, 95% CI, 0.09-0.20), and IBD flares (OR 0.44, 95% CI, 0.37-0.54), all P < .0001, compared with BS. Initiation of advanced IBD therapies was also lower in the GLP-1 RA group (OR 0.45, 95% CI, 0.33-0.61; P < .0001).

Despite a higher burden of comorbidities and a greater mean BMI, patients with obesity and IBD treated with GLP-1 RAs experienced significantly fewer gastrointestinal complications, thromboembolic events, disease flares, and surgical interventions compared with those undergoing BS. These findings suggest that GLP-1 RAs may represent a viable, less invasive therapeutic option for weight management and disease modulation in patients with obesity and IBD.