(1100) Risk for Cholecystitis in Patients Receiving Glucagon-like peptide-1 Receptor Agonists and Concomitant Gallstone-dissolution Agents: A Retrospective Cohort Study

Objectives: Incretin hormones, including glucagon-like peptide-1 (GLP-1), delay gallbladder emptying by suppressing cholecystokinin secretion, increasing risk for cholelithiasis. For this reason, GLP-1 receptor agonists (GLP-1RA) increase risk for cholelithiasis and cholecystitis. Ursodiol (ursodeoxycholate) and Chenodiol (chenodeoxycholate) are gallstone-dissolution agents (GDA), which can delay or prevent progression of cholelithiasis to cholecystitis. Currently, it is unclear whether the concomitant use of a GDA and GLP-1RA affects the incidence of cholecystitis in patients with cholelithiasis.

Methods: A retrospective cohort and time-to-event analysis was conducted for patients diagnosed with cholelithiasis (ICD10:K80) and were prescribed GLP-1 analogues (NLM:ATC:A10BJ) using the TriNetX electronic health record network. Cohort I included patients who were prescribed a concomitant GDA (RXNORM:2045735, 62427, 42588) and Cohort II excluded patients with current or past GDA use. The cohorts were then matched 1:1 using a propensity score matching algorithm that included fifteen covariates, such as: age, sex, race, gallbladder disorders (K87), past bariatric surgery, pertinent medications (estrogens, antimicrobials, fibrates), and others. The index date occurred when participants satisfied both diagnostic and medication exposure criteria and patients were observed for up to 365 days for incidence of cholecystitis (K81). A Kaplan Meier analysis and log-rank test were used to estimate and compare the incidence of cholecystitis between cohorts. Hazard ratios and 95% confidence intervals were calculated via proportional hazard model.

Results: After matching, there were 2,379 participants in each Cohort I and II. Patients were approximately 54 years old with similar proportions of male/female gender, weight class, history of bariatric surgery, etc. Patients in Cohort I (GLP-1RA + GDA) were 42% more likely to develop cholecystitis compared to those in Cohort II (GLP-1RA without GDA), HR 1.416 (95% CI 1.153, 1.741; p =0.0009). Results from the pre-match analysis were similar, HR 1.341 (95% CI 1.170, 1.537; p < 0.0001).

Conclusions: After matching, there was a significant increase in risk for development of cholecystitis in patients receiving a GLP-1RA with GDA compared to GLP-1RAs alone. These results are counter to expectations and may be better explained by confounders that were not included in our propensity score match. Additional studies are warranted to evaluate the effect of concomitant GLP-1RA and GDA use on the risk for development of cholecystitis.