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Peer-reviewedCC BY-NC 4.0BMJ Open Gastroenterology

Effect of metformin use in patients with type 2 diabetes mellitus on the risk of a first acute pancreatitis event, severe acute pancreatitis and progression to chronic pancreatitis: a cohort discovery study

  • Luis F Lara1
  • Mitchell Ramsey2
  • Maisam Abu-El-Haija3
  • Wei-Wen Hsu4
  • Inuk Zandvakili1
  • Moamen Gabr1
  • Andrew Ofosu1
  • Rosanne Danielson1
  • Milton Smith1
  • Georgios I Papachristou2
4 affiliations
  1. 1Internal Medicine, Division of Gastroenterology and Hepatology, University of Cincinnati, Cincinnati, Ohio, USA
  2. 2Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  3. 3Division of Pediatric Gastroenterology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
  4. 4Department of Biostatistics, Health Information and Data Sciences, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Abstract

Objective: Type 2 diabetes mellitus (T2DM) is a risk factor for acute pancreatitis (AP), severe AP (SAP) and chronic pancreatitis (CP). Metformin has anti-inflammatory and metabolic effects. We aimed to evaluate the effects of metformin on pancreatitis risk in patients with T2DM.

Methods: Retrospective cohort study using the US subset of the TriNetX network database. Subjects ≥18 years with T2DM, no prior pancreatitis and ≥12 months of metformin exposure were compared with a cohort with T2DM not on medication. The first AP event was recorded, SAP was defined using validated surrogates and CP was included if diagnosed ≥3 years after the first AP event. 1:1 propensity score matching was performed, and outcomes were compared using relative risk (RR).

Results: After matching, there were 74 930 subjects in each cohort. AP incidence was significantly lower among metformin users (268 (0.36%)) compared with non-users (420 (0.56%); RR 1.57, 95% CI 1.35 to 1.83; p<0.001). SAP occurred in 4664 (6.22%) metformin users versus 8399 non-users (RR 1.90, 95% CI 1.83 to 1.97; p<0.001). CP was less frequent in metformin users (98 (0.13%) vs 153 (0.23%); RR 1.56, 95% CI 1.21 to 2.01; p<0.001). Thirty-day mortality was significantly reduced in the SAP cohort (1.02% vs 2.02%; RR 2.00, 95% CI 1.84 to 2.19; p<0.0001), as was length of stay (6.09±12.72 vs 6.57±11.16 days; p<0.001), with no differences for AP or CP.

Conclusion: Metformin was associated with lower risks of AP, SAP and CP in subjects with T2DM, with a reduction in mortality and hospitalisation in patients with SAP. Metformin use may be a disease modifier in pancreatitis. Prospective studies are warranted to validate these observations, clarify dose–response relationships and explore mechanistic pathways.

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Cite

BibTeXRIS
BibTeX
@article{lara2026effect,
  title = {{Effect of metformin use in patients with type 2 diabetes mellitus on the risk of a first acute pancreatitis event, severe acute pancreatitis and progression to chronic pancreatitis: a cohort discovery study}},
  author = {Luis F Lara and Mitchell Ramsey and Maisam Abu-El-Haija and Wei-Wen Hsu and Inuk Zandvakili and Moamen Gabr and Andrew Ofosu and Rosanne Danielson and Milton Smith and Georgios I Papachristou},
  journal = {BMJ Open Gastroenterology},
  year = {2026},
  month = nov,
  doi = {10.1136/bmjgast-2026-002430},
  url = {https://doi.org/10.1136/bmjgast-2026-002430},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Effect of metformin use in patients with type 2 diabetes mellitus on the risk of a first acute pancreatitis event, severe acute pancreatitis and progression to chronic pancreatitis: a cohort discovery study
AU  - Luis F Lara
AU  - Mitchell Ramsey
AU  - Maisam Abu-El-Haija
AU  - Wei-Wen Hsu
AU  - Inuk Zandvakili
AU  - Moamen Gabr
AU  - Andrew Ofosu
AU  - Rosanne Danielson
AU  - Milton Smith
AU  - Georgios I Papachristou
PY  - 2026
DA  - 2026/11/03
JO  - BMJ Open Gastroenterology
DO  - 10.1136/bmjgast-2026-002430
UR  - https://doi.org/10.1136/bmjgast-2026-002430
AB  - Objective: Type 2 diabetes mellitus (T2DM) is a risk factor for acute pancreatitis (AP), severe AP (SAP) and chronic pancreatitis (CP). Metformin has anti-inflammatory and metabolic effects. We aimed to evaluate the effects of metformin on pancreatitis risk in patients with T2DM.  Methods: Retrospective cohort study using the US subset of the TriNetX network database. Subjects ≥18 years with T2DM, no prior pancreatitis and ≥12 months of metformin exposure were compared with a cohort with T2DM not on medication. The first AP event was recorded, SAP was defined using validated surrogates and CP was included if diagnosed ≥3 years after the first AP event. 1:1 propensity score matching was performed, and outcomes were compared using relative risk (RR).  Results: After matching, there were 74 930 subjects in each cohort. AP incidence was significantly lower among metformin users (268 (0.36%)) compared with non-users (420 (0.56%); RR 1.57, 95% CI 1.35 to 1.83; p<0.001). SAP occurred in 4664 (6.22%) metformin users versus 8399 non-users (RR 1.90, 95% CI 1.83 to 1.97; p<0.001). CP was less frequent in metformin users (98 (0.13%) vs 153 (0.23%); RR 1.56, 95% CI 1.21 to 2.01; p<0.001). Thirty-day mortality was significantly reduced in the SAP cohort (1.02% vs 2.02%; RR 2.00, 95% CI 1.84 to 2.19; p<0.0001), as was length of stay (6.09±12.72 vs 6.57±11.16 days; p<0.001), with no differences for AP or CP.  Conclusion: Metformin was associated with lower risks of AP, SAP and CP in subjects with T2DM, with a reduction in mortality and hospitalisation in patients with SAP. Metformin use may be a disease modifier in pancreatitis. Prospective studies are warranted to validate these observations, clarify dose–response relationships and explore mechanistic pathways.
SN  - 2054-4774
ER  -