Use of Biguanides and the Risk of Colorectal Cancer: A Register-Based Cohort Study
Lotte M. Knapen, Suzanne T.A.M. Dittrich, Frank de Vries, Jakob Starup-Linde, Peter Vestergaard, Ronald M.A. Henry, Leo M.L. Stolk, Cees Neef and Marloes T. Bazelier
Affiliation: Maastricht University Medical Centre, Department of Clinical Pharmacy and Toxicology, P. Debyelaan 25, 6228 HX Maastricht, The Netherlands.
Keywords: Biguanide, colorectal neoplasms, diabetes mellitus type two (T2DM), malignancies, metformin,
Observational studies have shown conflicting results on the potential protecting effect of biguanide use with the
risk of colorectal neoplasms. In addition, the cellular mechanism can either support or oppose biguanides influence on
colorectal carcinoma. Our objective was to evaluate the association between biguanide use and colorectal carcinoma. A
population-based cohort study using healthcare data from the Danish National database (1996-2007), was conducted. Oral
antidiabetic drug users (n = 177,281) were matched 1:3 with a population-based reference group. Cox proportional hazard
models estimated hazard ratios (HRs) of colorectal carcinoma. Stratification was performed to analyse the risk of
colorectal cancer in current biguanide users. Two sub-analyses were performed, to investigate the risk of colorectal cancer
associated with discontinuous and prolonged use of biguanides.
Instead of a protective effect, we found that current biguanide users had a 1.2-fold increased risk of colorectal cancer (HR
= 1.19, 95% CI = 1.08-1.30) as compared with the non-diabetes reference group. Prolonged use was not inversely
associated with colorectal cancer either. When studying colorectal risk with biguanides, the underlying T2DM should be
taken into account since a 1.3-1.6-fold increased risk was found in oral antidiabetic drug users compared to controls
unexposed to diabetic medication. This study could not detect a protective effect of biguanide use with colorectal cancer.
Therefore, this study does not support a further investigation of the effectiveness of biguanides to prevent colorectal
carcinoma in clinical studies.
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