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

  1. Samantha L. Bowker, MSC12,
  2. Sumit R. Majumdar, MD, MPH13,
  3. Paul Veugelers, PHD2 and
  4. Jeffrey A. Johnson, PHD12
  1. 1Institute of Health Economics, Edmonton, Alberta, Canada
  2. 2Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada
  3. 3Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
  1. Address correspondence and reprint requests to Dr. Jeffrey A. Johnson, #1200, 10405 Jasper Ave., Edmonton, AL, T5J 3N4 Canada. E-mail: jeff.johnson{at}


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.


  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted October 22, 2005.
    • Received August 18, 2005.
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