Metformin Is Associated With a Reduced Risk of Gastric Cancer, but Not Dysplasia, in Patients With Diabetes.

Objectives: Metformin has been suggested to exert chemopreventive effects against gastric cancer. However, epidemiologic evidence remains inconsistent, and its impact on histologically confirmed precursor lesions, such as gastric dysplasia, remains unclear. Methods: We conducted a retrospective observational study of patients with type 2 diabetes who underwent endoscopic biopsy at a tertiary hospital in South Korea between 2009 and 2018. The patients were categorized into four groups based on the use of metformin and insulin. Histologic outcomes, including gastric dysplasia and adenocarcinoma, were evaluated using endoscopic biopsy specimens. Logistic regression and survival analyses were performed to assess the association between the use of antidiabetic medications and outcomes of gastric neoplasia. Results: Among 5269 patients with diabetes who underwent endoscopic biopsy, metformin use without insulin was associated with a lower incidence of gastric adenocarcinoma than non-metformin use. By contrast, insulin use was associated with a higher incidence of gastric malignancies. The occurrence of premalignant lesions, including gastric dysplasia and intestinal metaplasia, did not differ significantly between medication groups. These findings were consistent across logistic regression and survival analyses. Conclusions: Metformin use was associated with a reduced risk of gastric cancer in patients with diabetes who were not receiving insulin, but did not reduce the occurrence of gastric dysplasia. These results suggest that metformin exerts a stage-specific effect on gastric carcinogenesis, primarily by inhibiting the progression from dysplasia to invasive carcinoma, rather than preventing the initial development of precursor lesions.