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Diabetes Care 29:254-258, 2006
DOI: 10.2337/diacare.29.02.06.dc05-1558
© 2006 by the American Diabetes Association
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Epidemiology/Health Services/Psychosocial Research
Original Article

Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin

Samantha L. Bowker, MSC1,2, Sumit R. Majumdar, MD, MPH1,3, Paul Veugelers, PHD2 and Jeffrey A. Johnson, PHD1,2

1 Institute of Health Economics, Edmonton, Alberta, Canada
2 Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada
3 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

Address correspondence and reprint requests to Dr. Jeffrey A. Johnson, #1200, 10405 Jasper Ave., Edmonton, AL, T5J 3N4 Canada. E-mail: jeff.johnson{at}ualberta.ca

OBJECTIVE—Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.

RESEARCH DESIGN AND METHODS—This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided.

RESULTS—We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 ± 1.9 years (means ± SD). The mean age for the cohort was 63.4 ± 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1–1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5–2.4; P < 0.0001).

CONCLUSIONS—Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.

Abbreviations: CDS, chronic disease score


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