P0810 Anti TNF Treatment is Associated with Reduced Risk of Diabetes in Patients With Inflammatory Bowel Disease
Authors: Shafrir A , Stokar J , Rubin D T 
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD) is a state of excess inflammatory cytokines, including tumor necrosis α (TNF). Studies in human and animal models showed that TNF has an important role in pathophysiology of insulin resistance (1). While there is some evidence of a link between IBD and diabetes mellitus (DM) and that anti-TNF therapy is associated with better glucose levels in patients with IBD and DM (2), the potential for prevention of onset or impact of other advanced therapies has not been described.

Methods
We used the TriNetX global federated network to identify patients with IBD ≥18 years diagnosed with IBD between 2019 and 2024, and who were treated with advanced therapy within 2 years of that diagnosis. Patients who were diagnosed with DM prior or within 3 months of IBD diagnosis or treatment were excluded.
The primary endpoint was a diagnosis of DM or a HgbA1C&gt;6.5%. Patients were divided into two different cohorts: 1) patients treated with anti-TNF, and 2) patients treated with vedolizumab, IL23 inhibitors or JAK inhibitors, and never with anti-TNF. Patients were compared using a 1:1 propensity matching by race, gender, age, sociodemographic comorbidities, BMI, hypertension, long term use of steroids, ischemic heart disease, IBD subtype and past total or partial colectomy. A diagnosis of psoriasis was used as positive control outcome, and a diagnosis of upper respiratory tract infections (URTI) was used as negative control outcome.

Results
43,372 patients with a new diagnosis of IBD were identified: 30,583 treated with anti TNF and 12,789 treated with other advanced therapies. Following propensity scored matching, 12,762 patients were in each balanced cohort. After a follow up of 3 years, patients treated with anti TNF had a 72.5% lower risk for subsequent diabetes (0.3% vs. 1.04% HR 0.275, 95% CI 0.174 -0.437, p&lt;0.001), a higher risk of psoriasis (HR 1.35, 95% CI 1.074 - 1.694, p&lt;0.001) but no significant difference of URTI (Figure 1).

Conclusion
Patients with IBD treated with anti-TNF have a significantly lower risk of developing diabetes compared to patients treated with other advanced therapies. The mechanisms and protective effect of anti-TNF therapy warrants further investigation.

References
1.Knobler, Hilla MD; Zhornicky, Taiba MD; Sandler, Alex MD; Haran, Nurit PhD; Ashur, Yafa MD; Schattner, Ami MD. Tumor Necrosis Factor–α–Induced Insulin Resistance May Mediate The Hepatitis C Virus–Diabetes Association. American Journal of Gastroenterology 98(12):p 2751-2756, December 2003. | DOI: 10.1111/j.1572-0241.2003.08728.x
2.Malini Gupta-Ganguli, Kyle Cox, Blake Means, Ivan Gerling, Solomon S. Solomon; Does Therapy With Anti–TNF-α Improve Glucose Tolerance and Control in Patients With Type 2 Diabetes?. Diabetes Care 1 July 2011; 34 (7): e121–121. https://doi.org/10.2337/dc10-1334

Figure 1 - Risk of Clinical Outcomes in Patients with IBD Treated with anti-TNF vs. Other Advanced Therapies in Propensity Matched Cohorts (n=12,762 in each cohort)