P4362 - A US Study on Incidence of Acute Pancreatitis, Severe Acute Pancreatitis and Mortality in Patients With Diabetes Mellitus Type 2 Taking Metformin

Luis Lara, MD¹, Wei-Wen Hsu, PhD¹, Rosanne Danielson, MD¹, Andrew Ofosu, MD, MPH², Milton Smith, MD¹, Inuk Zandvakili, MD, PhD¹, Moamen Gabr, MD, MSc¹, Mitchell L. Ramsey, MD³, Maisam Abu-El-Haija, MD⁴, Georgios I. Papachristou, MD, PhD³
1University of Cincinnati, Cincinnati, OH; 2University of Cincinnati College of Medicine, Cincinnati, OH; 3The Ohio State University Wexner Medical Center, Columbus, OH; 4Cincinnati Children's Hospital Medical Center, Cincinnati, OH

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 (Cambridge, MA) was queried from 2014-2025. 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 < ![if !supportAnnotations] >[AM1]< ![endif] > 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 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% females, 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. See table.

Discussion: 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.


Figure: Incidence of a first AP event and SAP and mortality in patients with DM 2 on metformin compared to DM 2 not taking metformin.

Disclosures:
Luis Lara: AbbVie – Consultant, Grant/Research Support, Speakers Bureau.
Wei-Wen Hsu indicated no relevant financial relationships.
Rosanne Danielson indicated no relevant financial relationships.
Andrew Ofosu indicated no relevant financial relationships.
Milton Smith indicated no relevant financial relationships.
Inuk Zandvakili: Eli Lilly – Consultant.
Moamen Gabr indicated no relevant financial relationships.
Mitchell Ramsey indicated no relevant financial relationships.
Maisam Abu-El-Haija indicated no relevant financial relationships.
Georgios Papachristou: AbbVie – Grant/Research Support.

Luis Lara, MD¹, Wei-Wen Hsu, PhD¹, Rosanne Danielson, MD¹, Andrew Ofosu, MD, MPH², Milton Smith, MD¹, Inuk Zandvakili, MD, PhD¹, Moamen Gabr, MD, MSc¹, Mitchell L. Ramsey, MD³, Maisam Abu-El-Haija, MD⁴, Georgios I. Papachristou, MD, PhD³. P4362 - A US Study on Incidence of Acute Pancreatitis, Severe Acute Pancreatitis and Mortality in Patients With Diabetes Mellitus Type 2 Taking Metformin, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.