title: Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.
abstract: OBJECTIVE
  Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study.
  
  
  METHODS
  Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes.
  
  
  RESULTS
  Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified.
  
  
  CONCLUSIONS
  Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.
authors.affiliation: Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Ruiter
authors.forename: L E
authors.initials: LE
authors.lastname: Visser
authors.forename: M P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.forename: J W W
authors.initials: JW
authors.lastname: Coebergh
authors.forename: H R
authors.initials: HR
authors.lastname: Haak
authors.forename: P H
authors.initials: PH
authors.lastname: Geelhoed-Duijvestijn
authors.forename: S M J M
authors.initials: SM
authors.lastname: Straus
authors.forename: R M C
authors.initials: RM
authors.lastname: Herings
authors.forename: B H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology; D015331:Cohort Studies; D003157:Community Pharmacy Services; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D010343:Patient Admission; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D061386:Insulin, Regular, Human; D000069036:Insulin Glargine