Metformin for Primary Colorectal Cancer Prevention in Patients With Diabetes: A Case-Control Study in a US Population

BACKGROUNDEmerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, to the authors' knowledge, none of these studies was conducted in a US population. Because environmental factors such as Western diet and obesity are implicated in the causation of CRC, a large case-control study was performed to assess the effects of metformin on the incidence of CRC in a US population. METHODSMarketScan databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to 2 controls matched for age, sex, and geographical region were selected for each case. Metformin exposure was assessed by prescription tracking within the 12-month period before the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AORs). RESULTSThe mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P=1.0). Approximately 60% of the study participants were male and 40% were female in each group. In the multivariable model, any metformin use was associated with a 15% reduction in the odds of CRC (AOR, 0.85; 95% confidence interval, 0.76-0.95 [P=.007]). After adjusting for health care use, the beneficial effect of metformin was reduced to 12% (AOR, 0.88; 95% confidence interval, 0.77-1.00 [P=.05]). The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure. CONCLUSIONSMetformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States. Cancer 2015;121:1071-1078. (c) 2014 American Cancer Society. The use of metformin is associated with a reduced risk of developing colorectal cancer among patients with diabetes in the US population. Further studies are needed to understand the mechanism of action and the development of metformin for clinical use.