Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis

Author:

Soranna Davide1,Scotti Lorenza1,Zambon Antonella1,Bosetti Cristina2,Grassi Guido3,Catapano Alberico4,La Vecchia Carlo256,Mancia Giuseppe3,Corrao Giovanni1

Affiliation:

1. a Dipartimento di Statistica, Unità di Biostatistica ed Epidemiologia, Università Milano-Bicocca, Milan, Italy;

2. c Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy;

3. b Dipartimento di Medicina Clinica e Prevenzione, Università Milano-Bicocca, Milan, Italy;

4. d Dipartimento di Scienze Farmacologiche, Università degli Studi di Milan, Milan, Italy;

5. e Dipartimento di Medicina del Lavoro, Università degli Studi di Milan, Milan, Italy;

6. f International Prevention Research Institute (IPRI), Lyon, France

Abstract

Abstract Objective. Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue. Materials and Methods. We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ2 statistics and measured with the I2 statistic. Publication bias was evaluated using funnel plot and Egger's regression asymmetry test. Results. Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metformin was associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54–0.70), colorectal cancer (0.64, 95% CI 0.54–0.76), and pancreatic cancer (0.38, 95% CI 0.14–0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site. Conclusions. Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.

Funder

Italian Ministry for University and Research

Italian Association for Research on Cancer

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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