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Document Type

Conference Proceedings

Abstract

Objective: To investigate the potential association between GLP-1 receptor agonists (semaglutide, tirzepatide) and the DPP-4 inhibitor (sitagliptin) with acute pancreatitis in patients with T2DM, addressing ongoing safety concerns surrounding their rapid clinical adoption. Methods: A retrospective cohort study was performed using Epic Cosmos, a de-identified multicenter EHR dataset of adults with T2DM (ICD-10-CM E11.) from 2015–2025. Patients with alcohol abuse or prior pancreatitis were excluded. Four mutually exclusive cohorts were established: non-users of GLP-1 RAs or DPP-4 inhibitors, semaglutide users, tirzepatide users, and sitagliptin users. The primary outcome was acute pancreatitis (ICD-10-CM K85.) within 12 months of drug initiation. Incidence, odds ratios (OR), and 95% confidence intervals (CI) were estimated using the non-user group as reference. Results: Acute pancreatitis occurred in 1.15% of non-users, 0.33% of semaglutide users, 0.20% of tirzepatide users, and 0.44% of sitagliptin users. Compared with non-users, the risk was significantly lower with semaglutide (OR 0.28, 95% CI 0.27–0.28), tirzepatide (OR 0.17, 95% CI 0.16–0.18), and sitagliptin (OR 0.38, 95% CI 0.37–0.39) (all p < 0.0001). Demographics were similar across cohorts. Conclusion: In this large real-world T2DM cohort, GLP-1 receptor agonist and DPP-4 inhibitor use were not associated with increased 12-month pancreatitis risk. Semaglutide, tirzepatide, and sitagliptin were instead linked to significantly lower incidence rates compared with non-users. These results indicate that incretin-based therapies may not elevate and could potentially reduce pancreatitis risk, warranting further mechanistic and longitudinal investigation.

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