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Background & AimsAntidiabetic drugs have been found to have various effects on cancer in experimental systems and in epidemiologic studies, although the association between these therapeutics and the risk of human pancreatic cancer has not been explored. We investigated the effect of antidiabetic therapies on the risk of pancreatic cancer. MethodsA hospital-based case-control study was conducted at M. D. Anderson Cancer Center from 2004 to 2008 involving 973 patients with pancreatic adenocarcinoma (including 259 diabetic patients) and 863 controls (including 109 diabetic patients). Information on diabetes history and other risk factors was collected by personal interview. The frequencies of use of insulin, insulin secretagogues, metformin, and other antidiabetic medications among diabetic patients were compared between cases and controls. The risk of pancreatic cancer was estimated using unconditional logistic regression analysis. ResultsDiabetic patients who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not taken metformin (odds ratio, 0.38; 95% confidence interval, 0.22–0.69; P = .001), with adjustments for potential confounders. This difference remained statistically significant when the analysis was restricted to patients with a duration of diabetes >2 years or those who never used insulin. In contrast, diabetic patients who had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer compared with diabetic patients who had not taken these drugs. ConclusionsMetformin use was associated with reduced risk, and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetic patients. Abbreviations used in this paper: BMI, body mass index, CI, confidence interval, DM2, type 2 diabetes mellitus, HbA1c, hemoglobin A1c, OR, odds ratio, TZD, thiazolidinedione ⁎ Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ‡ Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, Texas § Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Conflicts of interest The authors disclose no conflicts. Funding Supported by National Institutes of Health R01 grant CA98380 (to D.L.), SPORE P20 grant CA101936 (to J.L.A.), and a multidisciplinary research program grant from M. D. Anderson Cancer Center (to S.J.Y.). PII: S0016-5085(09)00555-1 doi:10.1053/j.gastro.2009.04.013 © 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
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ABSTRACT
Antidiabetic Therapies Affect Risk of Pancreatic Cancer