title: Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure.
abstract: OBJECTIVE
  We explored the relationship between glucose-lowering agents and cancer mortality rates in type 2 diabetes patients, hypothesising a decreased risk of cancer mortality with metformin use and a dose-risk gradient for insulin therapy.
  
  
  METHODS
  This was a population-based cohort study using administrative data from Saskatchewan Health, Canada. We identified new users of metformin or sulfonylureas from 1 January 1991 to 31 December 1996, with follow-up until death, departure from the province or 31 December 1999. Cox regression analyses were used to estimate the HR of death from cancer, accounting for time-varying exposure to metformin, sulfonylurea, and exogenous insulin therapy.
  
  
  RESULTS
  We identified 10,309 new users of metformin or sulfonylurea. The average follow-up was 5.4 (1.9) years, during which 407 (4.0%) cancer deaths occurred. Adjusting for age, sex and chronic disease score, the adjusted HR for metformin use was 0.80 (95% CI 0.65-0.98) compared with sulfonylurea monotherapy users. Adjusted HRs for subsequent insulin use were 2.22 (0.99-5.00), 3.33 (2.26-4.89) and 6.40 (4.69-8.73) for <3, 3 to 11 and > or = 12 insulin dispensations/year, respectively, compared with patients not on insulin. We observed a similar risk gradient among the sub-cohort of new insulin users.
  
  
  CONCLUSIONS
  Our results support previous reports of a decreased risk of cancer outcomes associated with metformin use relative to sulfonylurea monotherapy. We also provide new evidence of a gradient of cumulative insulin dispensations and cancer mortality rates.
authors.affiliation: Department of Public Health Sciences, School of Public Health, University of Alberta, 2-040 Health Research Innovation Facility, Edmonton, AB, Canada T6G 2E1.
authors.forename: S L
authors.initials: SL
authors.lastname: Bowker
authors.forename: Y
authors.initials: Y
authors.lastname: Yasui
authors.forename: P
authors.initials: P
authors.lastname: Veugelers
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000401:mortality*; D012525:Saskatchewan; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin
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