A Cohort Study of Metformin Exposure and Survival in Patients with Stage I–III Colorectal Cancer

Abstract

Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer-specific survival using population-level data. Adult patients with stage I-III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescription claims database. Multivariate Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prediagnostic metformin exposure (versus nonmetformin antidiabetic drugs) and colorectal cancer-specific mortality. Models were stratified by antidiabetic drug coprescription and intensity of metformin exposure. The cohort included 207 diabetics who received metformin, 108 diabetics not exposed to metformin, and 3,501 nondiabetic patients. In multivariate analyses, a nonsignificant reduction in colorectal cancer-specific mortality was observed for metformin-exposed patients relative to other treated diabetics (HR, 0.61; 95% CI, 0.37-1.01). In stratified analyses, no significant association was observed for patients receiving low-intensity metformin or metformin in combination with other antidiabetic drugs. High-intensity exclusive metformin use was associated with a significant reduction in colorectal cancer-specific mortality (HR, 0.44; 95% CI, 0.20-0.95). Significant associations between metformin exposure and colorectal cancer-specific mortality were observed only for high-intensity exclusive metformin use in the diabetic cohort. This study provides moderate evidence of an association between metformin exposure and improved colorectal cancer survival in a diabetic population. Additional studies in larger cohorts, with detailed information on diabetes severity, are required to confirm these results.