Long-term effectiveness of teduglutide in adults with short bowel syndrome and intestinal failure: interim analysis from a global multicenter registry

Background: Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, promotes intestinal adaptation in patients with short bowel syndrome requiring parenteral nutrition (PN).While its benefits in reducing PN dependence are well-documented, concerns persist regarding its long-term gastrointestinal (GI) safety, particularly the potential risks of colon polyps, neoplasia and small bowel (SB) obstruction.Understanding these risks is critical for optimizing treatment strategies and ensuring patient safety.Methods: We conducted a retrospective cohort study using the TriNetX federated research network to evaluate GI outcomes on 3 years follow up in PN-dependent adults receiving teduglutide for 1 year versus those not receiving it.Patients were compared using a 1:1 propensity score matching by race, gender, age, comorbidities, history of colonic polyps, short bowel syndrome, neoplasms, cholelithiasis and pancreas disease.The primary outcome was colonic polyps incidence; Secondary outcomes included colorectal carcinoma, SB pathology, and pancreatic or biliary diseases.Results: After matching, 302 patients were included in each cohort.There was no significant difference in the incidence of colonic polyps.However, small bowel obstruction was more common in the teduglutide group (14.6% vs. 7.0%, p=0.003).No small bowel malignancies or colorectal carcinoma were detected, pancreatic and biliary disease rates were similar between groups (table 1).Conclusions: Long-term teduglutide use is as reported prior is safe and did not increase the risk of colonic polyps, adenomas, or colorectal cancer.However, its association with higher SB obstruction rates warrants future studies to establish risk stratification mitigation strategies.To our knowledge this represents the largest study on long-term GI outcomes of teduglutide.