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Metformin, other antidiabetic drugs, and endometrial cancer risk: a nested case–control study within Italian healthcare utilization databases

Franchi, Matteo; Asciutto, Rosario; Nicotra, Federica; Merlino, Luca; La Vecchia, Carlo; Corrao, Giovanni; Bosetti, Cristina

European Journal of Cancer Prevention: May 2017 - Volume 26 - Issue 3 - p 225–231
doi: 10.1097/CEJ.0000000000000235
Research Papers: Gynecological Cancer

Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case–control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up. We used conditional logistic regression models to estimate the odds ratio (OR) of endometrial cancer in relation to use of antidiabetic drugs, adjusted for the Charlson’s comorbidity index, selected medical conditions, prescription of selected drugs, and concomitant use of other antidiabetic drugs. At cohort entry, no significant associations were observed for metformin [OR=0.99, 95% confidence interval (CI) 0.80–1.23], sulfonylureas (OR=1.14, 95% CI 0.91–1.42), insulin (OR=0.72, 95% CI 0.34–1.56), and other antidiabetic drugs (OR=1.21, 95% CI 0.75–1.95). When we considered use during follow-up, a borderline significant excess risk was found for metformin (OR=1.30, 95% CI 1.00–1.70). However, this estimate decreased to 1.07 (95% CI 0.82–1.41) when taking into account BMI using a Monte Carlo sensitivity analysis. No significant associations were found for sulfonylureas (OR=1.16, 95% CI 0.91–1.47), thiazolidinediones (OR=0.77, 95% CI 0.48–1.24), repaglinide (OR=1.32, 95% CI 0.94–1.87), incretins (OR=1.21, 95% CI 0.63–2.32), and insulin (OR=1.19, 95% CI 0.82–1.71). Our data indicate that metformin, insulin, and other antidiabetic drugs did not meaningfully affect the risk of endometrial cancer.

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aDepartment of Statistics, Unit of Biostatistics and Epidemiology, Università Milano-Bicocca

bUnità Organizzativa Governo dei Dati, delle Strategie e Piani del Sistema Sanitario, Regione Lombardia

cDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano

dDepartment of Epidemiology, IRCCS – Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan

eDepartment of Sciences for the Health Promotion and Mother and Child Care ‘G. D’Alessandro’, Hygiene Section, University of Palermo, Palermo, Italy

Correspondence to Cristina Bosetti, PhD, Department of Epidemiology, IRCCS – Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Giuseppe La Masa 19, 20156 Milan, Italy Tel: +39 023 901 4526; fax: +39 023 320 0231; e-mail:

Received October 14, 2015

Accepted January 9, 2016

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