Metformin use and the risk of colorectal adenoma: A systematic review and meta-analysis

Background and Aim: Although it is known that metformin can reduce risk of colorectal cancer, it is unclear whether it protects against colorectal adenoma. Methods: This study conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "colorectal," "colon," "rectal," "rectum," "adenoma," "polyp," "neoplasia," "neoplasm," "metformin," and "diabetes." Studies were included if they evaluated the association between metformin use and colorectal adenoma and reported odds ratios (ORs) or provided data from which these could be estimated. Results: Ten studies and a total of 8726 patients were evaluated. Across all studies, a median of 32.1% (range: 15.2-53.0%) of patients taking metformin also had adenoma; a median of 43.5% (range: 20.5-59.6%) of those not taking metformin had adenoma. In our meta-analysis, metformin use reduced the risk of adenoma (pooled OR = 0.76, 95% confidence interval [CI] = 0.63-0.92, I-2 = 60%). Upon subgroup analyses, metformin use tended to reduce risk of adenoma in a high-risk population consisting of patients with a history of colorectal neoplasia (CRN) (pooled OR = 0.61, 95% CI = 0.34-1.10, I-2 = 79%). In addition, metformin reduced the risk of adenoma in a high-risk population consisting of patients with diabetes mellitus (pooled OR = 0.75, 95% CI = 0.62-0.91, I-2 = 57%). Conclusion: Metformin use seemed to be associated with a reduced risk of colorectal adenoma, especially in high-risk populations consisting of patients with diabetes mellitus or a history of CRN, although statistical power was not achieved in patients with a history of CRN.