Risk of recurrent acute pancreatitis with GLP-1 receptor agonists after prior pancreatitis: a systematic review

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for patients with type 2 diabetes (T2D) and obesity. However, their safety in patients with prior pancreatitis remains uncertain. This systematic review aims to evaluate the risk of recurrent acute pancreatitis (RAP) associated with GLP-1 RA therapy. Methods We systematically searched for studies evaluating the safety of GLP-1 receptor agonists in adults with type 2 diabetes mellitus (T2DM) or obesity and a history of acute pancreatitis. The primary outcome was recurrent acute pancreatitis. We included studies of adults with prior acute pancreatitis treated with GLP-1 receptor agonists for type 2 diabetes, obesity, or related metabolic conditions. Studies without recurrent acute pancreatitis outcomes, pediatric populations, overlapping cohorts, insufficient data, or non-original publications were excluded. Results We included four studies comprising 10,624 patients, of whom 5,427 (51.0%) received GLP-1 receptor agonists. Two studies provided comparative data (5,224 GLP-1 RA users; 5,197 controls). GLP-1 receptor agonist use was associated with lower odds of recurrent acute pancreatitis than placebo (OR 0.26, 95% CI 0.05–1.32) and lower risk than SGLT2 inhibitor use (OR 0.57, 95% CI 0.52–0.64). Two additional studies provided recurrence rates among GLP-1 RA users with prior pancreatitis, reporting rates of 9.9% (95% CI 5.8%–16.3%) and 11.9% (95% CI 5.1%–25.8%). Conclusion Across the four included studies, GLP-1 receptor agonist use was not associated with an increase in RAP among patients with a prior history of acute pancreatitis. However, comparative evidence was limited to two studies, warranting cautious interpretation of these findings.