The Food and Drug Administration has upgraded the pregnancy risk category for NovoLog insulin from category C to B, based on the results of a large multinational study of pregnant women with type 1 diabetes.
The change was announced by the manufacturer, Novo Nordisk, early this year. NovoLog is the trade name for insulin aspart (rDNA origin) injection, a rapid acting insulin analogue that was approved by the FDA in 2000.
The study, conducted at 63 sites in 18 countries, compared NovoLog with regular human insulin in 322 pregnant women with type 1 diabetes. The study found that changes in HbA1c and the rate of maternal hypoglycemia were comparable in both groups, according to the company. The study was too small to make any conclusions about the risk of congenital malformations associated with NovoLog, according to a statement issued by Novo Nordisk.
The study also found that there was a reduced risk of neonatal hypoglycemia (glucose below 2.6 mmol/L) requiring treatment and “consistently low rates” of major maternal hypoglycemia and fewer preterm deliveries among the women treated with NovoLog, compared with those treated with regular human insulin.
Dr. Gideon Koren, director of the Motherisk Program, a teratogen information service at the Hospital for Sick Children, Toronto, said that he was pleased to see a decision based on a large, well-designed study. “This is more the exception than the rule, because very few such studies are being conducted and reported in pregnancy,” he noted in an interview.
“Insulin, being a very large molecule, is not expected to cross the human placenta, as was shown for regular insulin numerous times, and by us recently for insulin lispro,” added Dr. Koren, professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto.
Lispro, marketed by Eli Lilly as Humalog, is another rapid-acting human insulin analogue and is classified as pregnancy category B. The drug's label states that there are no adequate well-controlled studies in pregnant women, and that because animal reproduction studies “are not always predictive of human response,” the drug should be used during pregnancy only if clearly needed.
Gerald G. Briggs, B. Pharm., pharmacist clinical specialist, Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., noted in an interview that both insulin analogues are commonly used in pregnancy, but are usually reserved for type 1 diabetics, particularly those whose diabetes is considered difficult to control. He considers all insulins—human, pork, analogues, as well as inhaled insulin—as category B drugs, even though some are classified as C. All are large molecules that are closely related to human insulin and it is unlikely that insulin crosses the placenta, at least in clinically significant amounts, said Mr. Briggs, coauthor of the reference book “Drugs in Pregnancy and Lactation.”
A third insulin analogue on the market, insulin glulisine (Apidra), approved in 2004, has a pharmacokinetic profile that is similar to insulin aspart and lispro. Its label says that the effect of pregnancy on the drug's pharmacokinetics and pharmacodynamics has not been studied.
Under the current system of pregnancy risk categories used by the Food and Drug Administration, a drug is classified in category B if animal studies show no risk or human data are reassuring. A drug is classified as category C when animal studies have demonstrated adverse effects on the fetus, or have not been done, and studies in women are not available.