Protective Impact of GLP-1 Therapy on Post-ERCP Outcomes: A TriNetX Retrospective Cohort Analysis

Endoscopic retrograde cholangiopancreatography (ERCP) is essential for pancreaticobiliary disease management; however, there are risks associated with the procedure, particularly post-ERCP pancreatitis (PEP). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in metabolic disease, possess anti-inflammatory and cytoprotective properties that may influence periprocedural outcomes. Their impact on ERCP adverse events remains unclear; therefore, we aimed to investigate whether GLP-1 influences short-term postprocedural outcomes using a large real-world database.

We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults (18 y or older) who underwent ERCP between January 2015 and December 2024. Patients were categorized based on documented preprocedure GLP-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographic, clinical, procedural, and pharmacologic covariates to minimize confounding, yielding 2 well-balanced cohorts. Thirty-day post-ERCP outcomes-including acute pancreatitis, cholangitis, sepsis, gastrointestinal bleeding, biliary stricture, choledocholithiasis, and repeat ERCP-were assessed using ICD-10 and CPT codes. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were calculated.

Of 250,502 patients with ERCP screened, 21,818 propensity-matched individuals were included in the final analysis. Compared with matched nonusers, patients receiving GLP-1 receptor agonists had significantly lower 30-day rates of all major ERCP-related adverse events. GLP-1 RA exposure was associated with reduced risks of acute pancreatitis (RR: 0.47, 95% CI: 0.43-0.51), cholangitis (RR: 0.56, 95% CI: 0.50-0.62), sepsis (RR: 0.51, 95% CI: 0.46-0.57), gastrointestinal bleeding (RR: 0.49, 95% CI: 0.40-0.61), biliary stricture (RR: 0.52, 95% CI: 0.48-0.55), repeat ERCP (RR: 0.53, 95% CI: 0.48-0.58), and choledocholithiasis (RR: 0.66, 95% CI: 0.62-0.71). Results were consistent across time-to-event analyses over the 30-day follow-up period.

In this large real-world analysis, preprocedure GLP-1 RA therapy was associated with markedly reduced 30-day ERCP-related adverse events, most notably PEP. These findings highlight a potential protective role of GLP-1 signaling in the periprocedural inflammatory response and support prospective studies evaluating GLP-1 RAs as adjunctive prophylactic agents in ERCP. Further prospective studies are needed.