INTRODUCTION: Clinical studies have produced conflicting results on the effects of metformin on gastrointestinal cancer development. We aimed to investigate the association between metformin use and stomach, colon, liver, and pancreatic cancer development among patients with newly diagnosed, drug-naïve type 2 diabetes. METHODS: This retrospective study evaluated propensity score-matched patients with newly diagnosed type 2 diabetes from the Korean National Health Insurance Service database. Metformin users were categorized into tertiles according to the cumulative dose or duration of metformin treatment, and the risks of gastrointestinal cancers were compared. RESULTS: Metformin users had reduced risks of developing stomach cancer (hazard ratio [HR]: 0.841, 95% confidence interval [CI]: 0.797-0.887), colon cancer (HR: 0.865, 95% CI: 0.822-0.91), and liver cancer (HR: 0.709, 95% CI: 0.675-0.746; P < 0.001). However, metformin users did not have a reduced overall risk of pancreatic cancer (HR: 1.335, 95% CI: 1.209-1.475; P < 0.001). The risks tended to decrease at higher cumulative doses and durations of metformin use, with significantly reduced risks of all 4 cancers at the highest cumulative dose (‡1,200,000 mg) and the longest duration (‡2,000 days) of metformin use. DISCUSSION: This population-based data suggest that metformin could be associated with reductions in the risks of stomach, colon, and liver cancers, as well a reduced risk of pancreatic cancer in some subgroups. Metformin has benefit as a first-line treatment for type 2 diabetes mellitus. A further role in cancer risk reduction could be studied in controlled trials.
|Journal||Clinical and translational gastroenterology|
|Publication status||Published - 2020 Nov|
Bibliographical noteFunding Information:
Guarantor of the article: Sun Ok Song, MD, PhD. Specific author contributions: All authors contributed to the study design and were involved in all stages of manuscript development. J.H.Y. analyzed and interpreted data and drafted the manuscript. M.J.K. statistically analyzed and interpreted data. Y.Y.C., S.W.K., S.H.S., S.L., and Y.L. contributed to discussion. B.L. conceptualized and designed the study and contributed to discussion. S.O.S. conceptualized and designed the study, acquired data, analyzed and interpreted data, critically revised the manuscript for important intellectual content, and supervised the study. Financial support: This work was supported by the National Health Insurance Ilsan Hospital grant (2016-20-011). Potential competing interests: None to report.
© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology
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