Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes

Author:

Orchard Suzanne G1ORCID,Lockery Jessica E123ORCID,Broder Jonathan C1,Ernst Michael E4ORCID,Espinoza Sara5,Gibbs Peter67,Wolfe Rory1,Polekhina Galina1ORCID,Zoungas Sophia1,Loomans-Kropp Holli A38ORCID,Woods Robyn L1,McNeil John,Woods Robyn,Wolfe Rory,Murray Anne,Chan Andrew,Orchard Suzanne,Lockery Jessica,Nelson Mark,Reid Christorpher,Shah Raj,Newmann Anne,Storey Elsdon,Stocks Nigel,Tonkin Andrew,Espinoza Sara,

Affiliation:

1. School of Public Health and Preventive Medicine, Monash University , Melbourne,VIC, Australia

2. Translational Immunology and Nanotechnology Research Theme, School of Health and Biomedical Sciences, RMIT University , Bundoora, VIC, Australia

3. Department of Internal Medicine, Division of Cancer Prevention and Control, Ohio State University , Columbus, OH, USA

4. Department of Pharmacy Practice and Science, College of Pharmacy and Department of Family Medicine, Carver College of Medicine, The University of Iowa , Iowa City, IA, USA

5. Division of Geriatrics, Gerontology and Palliative Medicine, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, and Geriatrics Research, Education and Clinical Center, South Texas Veterans Health Care System , San Antonio, TX, USA

6. The Walter & Eliza Hall Institute of Medical Research, Royal Parade , Parkville, Melbourne, VIC, Australia

7. Department of Medical Oncology, Peter MacCallum Cancer Centre , Melbourne, VIC, Australia

8. Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute , Rockville, MD, USA

Abstract

AbstractBackgroundMetformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin’s impact on metformin users.MethodsAnalysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.ResultsOf 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).ConclusionsIn community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.ASPREE Trial RegistrationClinicalTrials.gov ID NCT01038583

Funder

National Institute on Aging

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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