Background Chronic hepatic complications are common in patients with short bowel syndrome–associated intestinal failure (SBS‐IF). Teduglutide, a glucagon‐like peptide‐2 analogue, demonstrated efficacy in reducing parenteral nutrition and/or intravenous fluid dependence among patients with SBS‐IF in phase 3 clinical studies. Methods This was a post hoc analysis of pooled data from two separate randomized, double‐blind, placebo‐controlled, multinational phase 3 clinical studies. Adult patients with SBS‐IF with parenteral nutrition and/or intravenous fluid dependence without liver disease at baseline were randomized to treatment with the glucagon‐like peptide‐2 analogue teduglutide (0.05 or 0.10 mg/kg/day) or placebo subcutaneously once daily for 24 weeks. Mixed‐effects models assessed the baseline predictors of change in liver chemistries. Results Between baseline and week 24, teduglutide treatment ( n = 109) was associated with least squares mean reductions in aspartate aminotransferase (–7.51 IU/L; P = 0.014), alanine aminotransferase (–12.15 IU/L; P = 0.002), and bilirubin (–5.03 µmol/L [–0.057 mg/dl]; P < 0.001) compared with that of the placebo ( n = 59). These values were independent of reductions in parenteral nutrition and/or intravenous fluid dependence. Conclusion Teduglutide treatment was associated with reductions in liver chemistries by week 24, which is beneficial for patients with SBS‐IF beyond improvements in parenteral nutrition and/or intravenous fluid dependence. Future studies should examine how long‐term teduglutide might mitigate the risk of liver disease in patients with SBS‐IF.
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