Harvey J Murff1,2,3, Christianne L Roumie4,5, Robert A Greevy4,6, Amber J Hackstadt6, Lucy E D'Agostino McGowan6, Adriana M Hung4,5, Carlos G Grijalva4,7, Marie R Griffin4,5,7. 1. Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA. Harvey.j.murff@vanderbilt.edu. 2. Department of Medicine, Vanderbilt University, Nashville, TN, USA. Harvey.j.murff@vanderbilt.edu. 3. Vanderbilt University Medical Center, 6012 Medical Center East, 1215 21st Avenue South, Nashville, TN, 37232, USA. Harvey.j.murff@vanderbilt.edu. 4. Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA. 5. Department of Medicine, Vanderbilt University, Nashville, TN, USA. 6. Department of Biostatistics, Vanderbilt University, Nashville, TN, USA. 7. Department of Health Policy, Vanderbilt University, Nashville, TN, USA.
Abstract
PURPOSE: Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes. METHODS: We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes. RESULTS: Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use. CONCLUSIONS: In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.
PURPOSE: Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes. METHODS: We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes. RESULTS: Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use. CONCLUSIONS: In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.
Authors: Christianne L Roumie; Adriana M Hung; Robert A Greevy; Carlos G Grijalva; Xulei Liu; Harvey J Murff; Tom A Elasy; Marie R Griffin Journal: Ann Intern Med Date: 2012-11-06 Impact factor: 25.391
Authors: Oystein Karlstad; Jacob Starup-Linde; Peter Vestergaard; Vidar Hjellvik; Marloes T Bazelier; Marjanka K Schmidt; Morten Andersen; Anssi Auvinen; Jari Haukka; Kari Furu; Frank de Vries; Marie L De Bruin Journal: Curr Drug Saf Date: 2013-11