MON-735 - Risk of Recurrent Acute Pancreatitis With Glucagon-like Peptide-1 Receptor Agonists in Patients With Prior History of Pancreatitis: A Systematic Review

Introduction:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity, and large meta-analyses have not shown an increased risk of acute pancreatitis in general populations. However, the safety of GLP-1 RAs in patients with a prior history of pancreatitis remains uncertain, as this high-risk group is frequently excluded from major studies. This systematic review with exploratory quantitative synthesis evaluated the risk of recurrent acute pancreatitis associated with GLP-1 RA use compared with control therapies or no exposure in adults with previous acute pancreatitis.

Methods:

Methods: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library from inception through March 2026 for randomized controlled trials and observational studies evaluating GLP-1 RA use in adults with prior history of acute pancreatitis. The search strategy combined terms related to GLP-1 RAs, acute pancreatitis, and recurrence. Studies were included if they reported outcomes in patients with documented prior acute pancreatitis exposed to GLP-1 RAs compared to control therapies. Statistical analyses were performed using Stata. When appropriate, effect estimates were combined as part of an exploratory quantitative synthesis. For comparative analyses, pooled effect estimates were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). For single-arm studies, pooled recurrence proportions were calculated using logit transformation with corresponding 95% CIs. Between-study heterogeneity was assessed using τ² (tau-squared). Sensitivity analyses were not performed due to the limited number of available comparative studies.

Results:
Four studies (3 observational and 1 randomized trial; N=10,624). The prevalence of type 2 diabetes, obesity, and other pancreatitis-related risk factors varied across studies. Two studies contributed to the comparative analysis (5,224 GLP-1 RA users and 5,197 controls), in which GLP-1 RA use was associated with lower odds of recurrent acute pancreatitis (OR 0.57; 95% CI 0.52–0.63; p < 0.001). In two single-arm studies of GLP-1 the pooled recurrence proportion was 10% (95% CI 7%–15%; p < 0.001). In adults with previous acute pancreatitis, GLP-1 RA therapy did not show an excess recurrence signal; however, comparative evidence was limited and largely driven by one observational study; therefore, findings should be interpreted cautiously.

Conclusion:
Our findings suggest that GLP-1 receptor agonists did not show an excess risk of recurrent acute pancreatitis in patients with a prior history of the disease. These results may support more individualized clinical decision-making in this high-risk population; however, comparative evidence remains limited, and further prospective studies are warranted to confirm these findings.

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