EP895 - Use of GLP-1 Agonists in Primary Sclerosing Cholangitis: Effects on Liver Function and Patient Outcomes

Purpose/Background: Primary sclerosing cholangitis (PSC) is an idiopathic condition of the biliary tree often linked to inflammatory bowel disease (IBD), characterized by inflammation and fibrosis which can progress to cholangiocarcinoma. With poorly understood pathophysiology and no approved therapies, clinical research and drug development has been challenging. Glucagon-like peptide-1 receptor agonist (GLP-1RA) medications have recently gained attention in IBD pathologies due to their anti-inflammatory effects, protection of the intestinal barrier, and promotion mucosal healing and pathogen defense. This is the first study to examine the outcomes of PSC patients exposed to GLP-1RAs.

Methods/Interventions: A multicenter retrospective review of patients with PSC diagnosis was conducted. Inclusion criteria were met if the patient had consistent FDA-approved GLP-1RA use and follow-up ≥6 months. Two equal observation periods were determined one year before and after initiation to compare outcomes. Changes in liver function tests (LFTs) were assessed using the Wilcoxon signed-rank test.

Results/Outcomes: From the 327 PSC patients identified among 5 hospitals, 7 had GLP-1RA use. All patients had either government-sponsored (43%) or private insurance (57%); none were self-pay. Four patients were excluded given < 6-month GLP-1RA exposure, with one due to gastrointestinal intolerance. Of the three that met inclusion criteria, all were male and never smoked. All were on ursodiol, and one was enrolled in the CM-101 SPRING trial for PSC. Of the seven FDA-approved GLP-1RAs, all were exposed to semaglutide alone. The peak dose prescribed ranged from 0.5-2.4 mg/week. Although none of the patients experienced cholangitis in the year before and after GLP-1RA initiation, the number of emergency department visits for right upper quadrant pain decreased from five in the year prior to zero in the year following initiation for all three patients. Two patients had pre/post-initiation magnetic resonance cholangiopancreatography (MRCP) that demonstrated no significant differences in bead-like biliary ductal dilatations (Figures 1 and 2). One patient's pre/post-initiation endoscopic retrograde cholangiopancreatography (ERCP) demonstrated persistent stricturing and ongoing bile duct inflammation on histopathology. There was no significant difference in AST (W=3.0, p=1.0), ALT (W=3.0 , p=1.0), alkaline phosphatase (W=1.0, p=0.5), and total bilirubin (W=1.0, p=0.5) peak levels at time of diagnosis of PSC and 1 year after initiation of GLP-1RA.

Conclusion/Discussion: This observational study is the first to evaluate outcomes in PSC patients following the initiation of GLP-1RA therapy. While there was a decrease in ED visits among all patients, there were no meaningful changes in LFTs or imaging after GLP-1RA initiation. Further research will be needed to assess the impact of GLP-1RA therapy on PSC progression.

Figure 1.
Magnetic resonance cholangiopancreatography (MRCP) images of a patient with primary sclerosing cholangitis (PSC), captured one year before and after initiation of GLP-1 receptor agonist (GLP-1RA) therapy. While pre-therapy imaging suggested active cholangitis and ductal irregularities, post-therapy imaging revealed more extensive ductal stricturing, peribiliary inflammation, and early signs of architectural remodeling such as fibrosis, nodularity, and lobulated liver contour. These findings suggest ongoing PSC disease activity without clear radiologic improvement following GLP-1RA therapy.
Figure 2.
MRCP images for a second patient with PSC from one year before and after initiation of GLP-1RA therapy, with no significant interval change in the biliary architecture. The persistent ductal irregularities and stricturing are consistent with the chronic nature of PSC.