title: Further exploration of the relationship between insulin glargine and incident cancer: a retrospective cohort study of older Medicare patients.
abstract: OBJECTIVE
  In vitro evidence suggests insulin glargine promotes tumors; observational human studies are conflicting. We aimed to expand understanding of this potential treatment risk.
  
  
  METHODS
  This retrospective cohort study of type 2 diabetic patients >68 years old used Medicare inpatient, outpatient (2003-2008), and prescription data (2006-2008). Adjusting for patient characteristics, dose, and metformin use, Cox models yielded hazard ratios (HRs) for incident cancer (breast, prostate, pancreas, colon, any site) associated with three forms of insulin: nonglargine, glargine, or glargine plus nonglargine (combination).
  
  
  RESULTS
  Overall, 81,681 patients were followed for a mean of 23.1 months. Mean age was 77.4 years. Treatment group distribution was 20.7% glargine, 60.5% nonglargine, 18.7% combination insulin. We observed 5,466 incident cancers; crude rates did not vary by treatment group. In fully adjusted models, nonglargine use was the referent; glargine was not associated with significant increased risk of any cancer measure. In secondary analyses including only the top quartile of daily insulin dose patients, glargine was not associated with any cancer risk difference; combination insulin was associated with higher breast cancer risk (HR 1.75 [95% CI 1.10-2.78]) and lower colon cancer risk (0.33 [0.13-0.80]). In age-stratified analyses of highest-dose users, combination insulin conferred a higher risk of breast cancer in those ≤75 years old (2.87 [1.45-1.59]).
  
  
  CONCLUSIONS
  The general lack of association between glargine-only use and cancer is reassuring. Breast cancer risk associated with high-dose combination insulin in secondary analyses could result from multiple comparisons, residual confounding, or true association; further research is warranted.
authors.affiliation: Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA. nancy.e.morden@dartmouth.edu
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Morden
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Liu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smith
authors.forename: Todd A
authors.initials: TA
authors.lastname: Mackenzie
authors.forename: Jonathan
authors.initials: J
authors.lastname: Skinner
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000139:chemically induced; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006801:Humans; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000139:chemically induced*; D012189:Retrospective Studies
chemical_list: D049528:Insulin, Long-Acting; D000069036:Insulin Glargine