Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis.
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.


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 χ(2) statistics and measured with the I(2) 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.
Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, Italy.
Davide
D
Soranna
Lorenza
L
Scotti
Antonella
A
Zambon
Cristina
C
Bosetti
Guido
G
Grassi
Alberico
A
Catapano
Carlo
C
La Vecchia
Giuseppe
G
Mancia
Giovanni
G
Corrao
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008687:Metformin / Q000009:adverse effects*; D009369:Neoplasms / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin