Abstract 2295: Association between metformin use and the risk of colorectal adenomas: A systematic review and meta-analysis
Authors: Hardikar Sheetal , Li Jessica S. , He Qianchuan , Kocarnik Jonathan , Boyko Edward J. , Newcomb Polly A. 
Published: July 2017

Abstract
Metformin, the most commonly prescribed drug in type-2 diabetes, has been evaluated for its potential cancer chemopreventive role. While evidence from meta-analyses suggests a reduced risk for colorectal cancer in association with metformin use, recent European studies have reported no association between metformin and colorectal cancer risk. For precursors to colorectal cancers such as colorectal adenomas, however, literature evaluating their relationship with metformin use is sparse. We performed a systematic review and meta-analysis of available studies to quantitatively assess the association of metformin use with risk of colorectal adenomas. In accordance with PRISMA guidelines and using relevant MeSH terms, we searched the PubMed, EMBASE, and Web of Science databases through September 30, 2016 to identify full-text articles investigating the risk for colorectal adenomas associated with the use of metformin. Overall risk ratios (RR) and 95% confidence intervals (CI) for colorectal adenomas were calculated using a fixed-effects model. Heterogeneity between studies was evaluated using the Cochrane’s Q- test and the I2- statistic. Potential publication bias was assessed by constructing a funnel plot. Sub-group analyses were performed to examine whether the association with metformin use differed by country/region. Of the 609 articles identified through searching the three databases, 6 studies were eligible for our meta-analysis (1 randomized trial, 2 case-control, and 3 cohort studies; 4 Asian studies and 2 US-based studies) and contributed a total of 9613 patients. The meta-analysis suggested that the risk for colorectal adenomas was significantly lower among metformin users as compared to non-users [overall RR (95% CI): 0.69 (0.62-0.77), test for overall effect Z =18.52, P-value &lt;0.0001]. This protective risk applied both for studies within the US and Asian regions [pooled RRs (95% CI): 0.72 (0.64-0.81) and 0.62 (0.47-0.76), respectively]. There was no heterogeneity observed between studies (Q-test p= 0.09, I2-statistic 47.3%) and no evidence of any publication bias on funnel plot visualization. This meta-analysis indicates that the use of metformin is significantly associated with a lower risk of colorectal adenomas. As metformin is an affordable and well-tolerated drug, it has the potential to be an effective agent for polyp chemoprevention. Further long-term randomized controlled trials are needed to confirm the anti-neoplastic effects of metformin in reducing the risk of colorectal polyps, and eventually colorectal cancer, in the general population.
Citation Format: Sheetal Hardikar, Jessica S. Li, Qianchuan He, Jonathan Kocarnik, Edward J. Boyko, Polly A. Newcomb. Association between metformin use and the risk of colorectal adenomas: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2295. doi:10.1158/1538-7445.AM2017-2295