title: Combined randomised controlled trial experience of malignancies in studies using insulin glargine.
abstract: OBJECTIVE
  Recent publications of data extracted from population registries have suggested a possible relationship between treatment with insulin glargine and increased incidence of cancer/breast cancer. The aim of the present study was investigate this possible relationship using data from the manufacturer's (sanofi-aventis) pharmacovigilance database.
  
  
  METHODS
  We analysed the manufacturer's (sanofi-aventis) pharmacovigilance database for all randomised clinical trials (RCTs; Phase 2-4) comparing insulin glargine with any comparator in type 1 or type 2 diabetes. We identified all serious adverse events coded under the System Organ Class of 'neoplasms, benign, malignant and unspecified'. Treatment-emergent neoplasms judged to be malignant were included in this analysis.
  
  
  RESULTS
  The database included 31 studies, 12 in type 1 diabetes and 19 in type 2 diabetes. Twenty compared insulin glargine with NPH insulin, 29 were parallel-group studies and two had a crossover design. Studies were generally of 6 months' duration, except for trial reference number 4016 (n = 1,017), which had a duration of 5 years. Overall, 10,880 people were included in the analysis (insulin glargine, 5,657; comparator, 5,223). Forty-five people (0.8%) vs 46 people (0.9%) reported 52 and 48 cases of malignant cancer in the insulin glargine and comparator groups, respectively (RR 0.90, 95% CI 0.60-1.36). Skin (12 people with 16 events vs six people with seven events, RR 1.85, 95% CI 0.69-4.92), colon and rectum (six vs ten people, RR 0.55, 95% CI 0.20-1.52), breast (four vs six people, RR 0.62, 95% CI 0.17-2.18) and gastrointestinal tract (six vs four people, RR 1.38, 95% CI 0.39-4.90) were the most commonly reported sites.
  
  
  CONCLUSIONS
  In these 31 RCTs, insulin glargine was not associated with an increased incidence of cancer, including breast cancer, compared with the comparator group.
authors.affiliation: ICM-Diabetes, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. philip.home@newcastle.ac.uk
authors.forename: P D
authors.initials: PD
authors.lastname: Home
authors.forename: P
authors.initials: P
authors.lastname: Lagarenne
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016208:Databases, Factual; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D007336:Insulin, Isophane