Work

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

Year: 2026

Type: article

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.

Source: BMJ Open Gastroenterology

DOI: 10.1136/bmjgast-2026-002430