A Cohort Study of Metformin Exposure and Survival in Patients with Stage I-III Colorectal Cancer
Spillane S, Bennett K, Sharp L, Barron T
Background: 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.
Methods: Adult stage I-III colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. Use of metformin and other anti-diabetic 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 pre-diagnostic metformin exposure (versus non-metformin anti-diabetic drugs) and colorectal cancer-specific mortality. Models were stratified by anti-diabetic drug co-prescription and intensity of metformin exposure.
Results: The cohort included 207 diabetics who received metformin, 108 diabetics not exposed to metformin, and 3501 non-diabetic patients. In multivariate analyses a non-significant 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 anti-diabetic 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).
Conclusions: Significant associations between metformin exposure and colorectal cancer-specific mortality were observed only for high intensity exclusive metformin use in the diabetic cohort. Impact: 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.
