Journal Article

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

Jeffrey A. Johnson, Sumit R. Majumdar, Samantha L. Bowker, Paul Veugelers

2006

Overview

Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin Samantha L. Bowker , MSC 1 2 , Sumit R. Majumdar , MD, MPH 1 3 , Paul Veugelers , PHD 2 and Jeffrey A. Johnson , PHD 1 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 Abstract 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. CDS, chronic disease score Footnotes 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. DIABETES CARE

• Publisher: American Diabetes Association
• Subject: Aged / Biological and medical sciences / Cancer / Cohort analysis / Cohort Studies / Comorbidity / Diabetes / Diabetes Mellitus, Type 2 - drug therapy / Diabetes. Impaired glucose tolerance / Drug therapy / Drug Therapy, Combination / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Epidemiology / Female / Follow-Up Studies / Humans / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - therapeutic use / Insulin / Insulin - adverse effects / Insulin - therapeutic use / Male / Medical sciences / Metformin - adverse effects / Metformin - therapeutic use / Middle Aged / Mortality / Multivariate Analysis / Neoplasms - etiology / Neoplasms - mortality / Proportional Hazards Models / Retrospective Studies / Risk Factors / Saskatchewan / Severity of Illness Index / Sulfonylurea Compounds - adverse effects / Sulfonylurea Compounds - therapeutic use / Type 2 diabetes