S284 A United States Study on Incidence of Acute Pancreatitis, Severe Acute Pancreatitis and Mortality in Patients With Diabetes Mellitus Type 2 Taking Metformin

Introduction: Subjects with diabetes mellitus (DM) have a higher risk of developing acute pancreatitis (AP), and some will develop severe AP (SAP) with associated mortality. Metformin is regularly used to treat Type 2 DM (T2D) by increasing peripheral glucose uptake and insulin secretion and decreasing gluconeogenesis. It also has anti-inflammatory properties via NFkB inhibition directly by AMPK or indirectly by PTEN, a notable cascade activated in AP. We studied the effect of metformin on the incidence of AP in patients with T2D. Methods: The TriNetX database was queried from 2014 to 2025. Only data from the Unites States was used. Inclusion criteria were patients on metformin for at least 1 year before the index AP episode. We applied 37 exclusion criteria such as a previous history of AP, CP, pancreas surgery, alcohol and tobacco use, and Type 1 DM to homogenize the study group. AP was diagnosed using ICD-10 codes. Severe AP was established using ICD-10 codes for renal and respiratory failure and shock. Propensity score matching (PSM) was performed after adjusting variables using Wilcoxon rank sums and Kruskal-Wallis test. Percentages and odds ratio (OR) were reported. P < 0.001 was considered significant. Results: Before matching there were 76,096 subjects with DM 2 on metformin and 1,943,565 with DM 2 not on metformin. After PSM there were 74,930 subjects in each group. 53% women, 58% White, 17% Black, mean age 60. Patients on metformin were significantly less likely to have a first AP event, 3.6%, or SAP, 6.2% compared to those not taking metformin, 5.7%, and 11%; OR 1.59 and OR 1.81, respectively; P < 0.0001. Mortality was borderline lower for subjects with AP on metformin (OR 1.64); P = 0.001. Mortality was significantly lower for patients with SAP on metformin, 10.2%, compared to those not on metformin, 21%, respectively, OR 2.08; P < 0.0001. Conclusion: The decreased incidence of AP and SAP in subjects with T2D on metformin compared to non-users seen in our study may be explained by the inhibiting effect of metformin on the inflammatory cascade. There was also a significant decrease in mortality when patients on metformin developed SAP. The benefits of metformin in this patient population should be explored further.