Insulin Glargine Safety in Pregnancy

The objective of this study was to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique.

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 μU/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 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.

The results obtained from perfusions carried out at therapeutic insulin glargine concentrations suggest that insulin glargine does not cross the human placenta to a measurable extent. Transport across the placenta was demonstrated at concentrations 1,000-fold higher than therapeutic levels. Even at these very high levels, there was a 100-fold difference in the rate of disappearance from the maternal compartment and the rate of appearance in the fetal compartment. This difference between insulin uptake and insulin transferred to the fetal compartment probably corresponds to the clearance of insulin by placental tissue. These data suggest that the placenta is able to sequester and/or metabolize insulin glargine at concentrations up to 1,000-fold higher than therapeutic levels, thereby limiting its entry into the fetal compartment. The limited transfer of insulin glargine across the placenta is supported by previous research findings. Although the liver and kidney are the major sites of insulin clearance, the placenta has been shown to possess receptors for insulin as well as a capacity for rapid degradation by insulin-degrading enzymes.

In summary, when used at therapeutic concentrations, insulin glargine is not likely to cross the placenta. Results indicate a wide capacity of the human placenta to block insulin glargine transfer to the fetal compartment.

Diabetes Care. 2010;33(1):29-33