title: Effect of Long-Acting Insulin Analogs on the Risk of Cancer: A Systematic Review of Observational Studies.
abstract: OBJECTIVE
  Observational studies examining the association between long-acting insulin analogs and cancer incidence have produced inconsistent results. We conducted a systematic review of these studies, focusing on their methodological strengths and weaknesses.
  
  
  METHODS
  We systematically searched MEDLINE and EMBASE from 2000 to 2014 to identify all observational studies evaluating the relationship between the long-acting insulin analogs and the risk of any and site-specific cancers (breast, colorectal, prostate). We included cohort and case-control studies published in English on insulin glargine and detemir and any cancer incidence among patients with type 1 or 2 diabetes. The methodological assessment involved the inclusion of prevalent users, inclusion of lag periods, time-related biases, and duration of follow-up between insulin initiation and cancer incidence.
  
  
  RESULTS
  A total of 16 cohort and 3 case-control studies met our inclusion criteria. All studies evaluated insulin glargine, and four studies also examined insulin detemir. Follow-up ranged from 0.9 to 7.0 years. Thirteen of 15 studies reported no association between insulin glargine and detemir and any cancer. Four of 13 studies reported an increased risk of breast cancer with insulin glargine. In the quality assessment, 7 studies included prevalent users, 11 did not consider a lag period, 6 had time-related biases, and 16 had short (<5 years) follow-up.
  
  
  CONCLUSIONS
  The observational studies examining the risk of cancer associated with long-acting insulin analogs have important methodological shortcomings that limit the conclusions that can be drawn. Thus, uncertainty remains, particularly for breast cancer risk.
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Division of Clinical Epidemiology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Doll
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Division of Clinical Epidemiology, Department of Medicine, McGill University, Montreal, Quebec, Canada samy.suissa@mcgill.ca.
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced*; D064887:Observational Studies as Topic; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting