S281 Correlation Between Statin Use and the Incidence of Acute Pancreatitis in Patients With Diabetes: A Global Database Study

Introduction: Statins are widely used to control serum lipids and reduce the risk of cardiovascular events. Common side-effects include myalgias, hepatotoxicity, proteinuria, and diabetes which are usually offset by the benefit. These medications have anti-inflammatory effects including down-regulation of pro-inflammatory cytokines. They have also been used to prevent post-endoscopic retrograde cholangiopancreatography acute pancreatitis (AP), and to prevent development of diabetes after AP, but an increased risk of AP in patients on statins has also been reported, without a clear mechanism of action. We studied the correlation with statin use and the risk of AP and severe AP (SAP) in patients with type 2 diabetes mellitus (DM2). Methods: We used the global research database TriNetX which comprises over 315 million individual electronic medical records providing de-identified data. For this analysis data from 2014 to 2024 were compiled, and >85% of the patients were from the United States. Adult patients (>18 years) with DM2 were included in the analysis and comprehensive exclusion criteria (39 total) were made to homogenize the comparison groups and to control confounders. Patients had no previous pancreatic disease and had to be on any statins for at least 1 year and were followed longitudinally. The cohorts were 1:1 propensity score matched for age sex, race, body weight, and smoking status. Results: After matching, each cohort had 138,008 patients. The average age was 66.2 12.2 (SD), there were 47% women in each group, and 19.3% were African Americans. The risk of AP was similar, 0.275% in patients on statins and 0.337% in patients not on statins, RR 1.227, 95% CI 1.07-1.41, P = 0.003. However, patients with DM2 that were not on statins had a decreased risk of developing severe AP, RR of 0.906, 95% CI 0.88-0.93, P < 0.0001. Both groups had a similar need to undergo endoscopic retrograde cholangiopancreatography (RR of 1.33, 95% CI 1.06-1.67, P = 0.0136). Conclusion: In this retrospective cohort, the risk of AP was similar in patients with DM2 on statins. Interestingly, patients with DM2 on statins were more likely to develop SAP. It is not clear if this was associated with transient or persistent SAP or if it resulted in poorer outcomes. The effect of variables including medical history, and concomitant drug interactions may play a role in this perceived increased association. Statins metabolized by CYP3A4 may be more pancreato-toxic, so the type and dose of statin may play a role. More evidence to include statins as a cause of drug induced AP or SAP is necessary.