Insulin Glargine Safety in Pregnancy: a Transplacental Transfer Study

  1. Erika K. Pollex, BMSc1,2,
  2. Denice S. Feig, MD3,
  3. Angelika Lubetsky1,
  4. Paul M. Yip, PhD4 and
  5. Gideon Koren, MD (gkoren{at}sickkids.ca)1,2
  1. 1Division of Clinical Pharmacology and Toxicology, the Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada
  3. 3Division of Endocrinology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and
  4. 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Abstract

    Objective: Insulin glargine (Lantus, Aventis Pharmaceuticals) is an extended-action insulin analogue with greater stability and duration of action compared to regular human insulin. The long duration of action and decreased incidence of hypoglycemia provide potential advantages for its use in pregnancy. However, the placental pharmacokinetics of insulin glargine have not been studied. Therefore, the objective of this study is to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique.

    Research Design and Methods: Placentae were obtained with informed consent following elective cesarean section delivery of non-complicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/L (20μU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1000-fold higher than therapeutic levels (150, 225, 300 nmol/L). A subsequent perfusion was completed for further confirmation of findings where the maternal circuit remained open and insulin glargine was continuously infused at 150pmol/L. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay.

    Results: Results from perfusions carried out at therapeutic concentrations (150pmol/L) of insulin glargine showed no detectable insulin glargine in the fetal circuit. Following perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/L, the rate of transfer remained low, 0.079 ± 0.01, 0.14 and 0.064 pmol/min/g tissue respectively.

    Conclusions: Insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta.

    Footnotes

      • Received June 8, 2009.
      • Accepted September 14, 2009.

    This Article

    1. Diabetes Care
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