Combined randomised controlled trial experience of malignancies in studies using insulin glargine

Diabetologia. 2009 Dec;52(12):2499-506. doi: 10.1007/s00125-009-1530-5. Epub 2009 Sep 15.

Abstract

Aims/hypothesis: 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/interpretation: In these 31 RCTs, insulin glargine was not associated with an increased incidence of cancer, including breast cancer, compared with the comparator group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Databases, Factual
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Isophane / therapeutic use
  • Insulin, Long-Acting
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Random Allocation
  • Randomized Controlled Trials as Topic

Substances

  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin, Isophane