New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes
- Gillian Libby, MSc,
- Louise A Donnelly, BSc,
- Dr Peter T Donnan, PhD,
- Professor Dario R Alessi, PhD,
- Professor Andrew D Morris, FRCP and
- Dr Josie MM Evans, PhD (j.m.m.stansfield{at}cpse.dundee.ac.uk)
- Research Statistician, Division of Clinical & Population Sciences and Education, University of Dundee
- Statistician, Division of Clinical & Population Sciences and Education, University of Dundee
- Professor of Epidemiology and Biostatistics, Division of Clinical & Population Sciences and Education, University of Dundee
- Principal Investigator, School of Life Sciences, University of Dundee
- Professor of Diabetic Medicine, Diabetes Research Centre, University of Dundee
- Senior Lecturer in Epidemiology, Division of Clinical & Population Sciences and Education, University of Dundee
Abstract
Objectives: The anti-diabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumour formation and inhibit cell growth, in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes.
Research Design and Methods: In an observational cohort study using record-linkage databases, based in Tayside, Scotland, UK, we identified people with type 2 diabetes who were new users of metformin in 1994-2003. We also identified a set of diabetic comparators, individually matched to the metformin users by year of diabetes diagnosis, who had never used metformin. In a survival analysis we calculated hazard ratios for diagnosis of cancer, adjusted for baseline characteristics of the two groups using Cox regression.
Results: Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 years and 2.6 years respectively (p < 0.001). The unadjusted hazard ratio for cancer was 0.46 (0.40–0.53). After adjusting for sex, age, BMI, HbA1c, deprivation, smoking and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53–0.75).
Conclusions: These results suggest that metformin use may be associated with a reduced risk of cancer. A randomized trial is needed to assess whether metformin is protective in a population at high risk for cancer.
Footnotes
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- Received December 5, 2008.
- Accepted May 30, 2009.
- Copyright © American Diabetes Association
