Insulin glargine safety in pregnancy: a transplacental transfer study

Abstract

Objective: Insulin glargine (Lantus) is an extended-action insulin analog with greater stability and duration of action than 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 was 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 after elective cesarean section delivery of noncomplicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/l (20 microU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1,000-fold higher than therapeutic levels (150, 225, and 300 nmol/l). A subsequent perfusion for which the maternal circuit remained open and insulin glargine was continuously infused at 150 pmol/l was completed for further confirmation of findings. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay.

Results: Results from perfusions carried out at therapeutic concentrations (150 pmol/l) of insulin glargine showed no detectable insulin glargine in the fetal circuit. After perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/l, the rate of transfer remained low at 0.079 +/- 0.01, 0.14, and 0.064 pmol . min(-1) . g tissue(-1), respectively.

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

Figure 1

Maternal and fetal insulin concentrations during 3-h perfusions in the presence of therapeutic levels (150 pmol/l) of insulin glargine (n = 5). ▼, maternal open circuit; ■, maternal closed circuit; ●, fetal.

Figure 2

Disappearance of insulin from the maternal compartment over 180 min of perfusion in the presence of insulin glargine concentrations 1,000-fold greater than therapeutic (150–300 nmol/l) (n = 4). ■, maternal reservoir concentration 150 nmol/l; ●, maternal reservoir concentration 300 nmol/l; ▲, maternal reservoir concentration 150 nmol/l; ♦, maternal reservoir concentration 225 nmol/l.

Figure 3

Appearance of insulin in the fetal compartment after perfusions in the presence of maternal insulin glargine concentrations 1,000-fold greater than therapeutic (150–300 nmol/l) (n = 4). ■, maternal reservoir concentration 150 nmol/l; ●, maternal reservoir concentration 300 nmol/l; ▲, maternal reservoir concentration 150 nmol/l; ♦, maternal reservoir concentration 225 nmol/l.