Now the Food and Drug administration (FDA) has given the go ahead to revising the drug classification for Levemir® (insulin detemir), giving health care providers and patients another insulin choice.
NPH is an intermediate acting insulin that begins working in 90 minutes to 4 hours, peaks between 4 to 12 hours and has an overall duration of 24 hours (although practically lasts about 16 to18 hours). Because it is a human insulin with the same amino acid structure as the insulin in our bodies, it is considered safe for use in pregnancy. Women with diabetes prior to beginning pregnancy usually take two injections per day, while those who contract gestational diabetes can often achieve metabolic control with one injection in the evening.
Although effective, NPH has a number of drawbacks that have reduced its use as insulin-of-choice for the general population. Its action time is quite variable from day to day, which can make it difficult to achieve optimal glucose control. So even if activity and food intake is controlled for, significant blood glucose fluctuations can still occur.
And unlike today’s more common basil insulins, NPH has a peak or extra punch hours after injection. Often this requires that patients eat a snack to avoid the possibility of low blood glucose.
Levemir®, on the other hand, offers the possibility of one injection per day and avoids the issue of timing for snacks. Pregnant women with diabetes, unlike the general adult population with diabetes, still need snacks in order to consume adequate carbohydrate and protein for fetal growth. And unlike NPH, it has a more consistent day-to-day action curve.
In a randomized controlled study, researchers compared NPH and Levemir® in 310 pregnant women with type 1 diabetes. The results of the study have not been formally published yet so it is difficult to review the basis of the FDA’s decision, which gives some doctors pause.
“Before I start using Levemir®, I will want to see data that shows that Levemir is just as safe and just as effective as NPH insulin which is currently the preferred basal insulin for women who take insulin injections,” said says Florence Brown, M.D., Co-director of the Joslin and Beth Israel Deaconess Medical Center Diabetes in Pregnancy Program.
“In terms of safety, I would like to see that it is safe from a metabolic stand point (e.g. no increase in serious high or low glucoses) and that there are no increased adverse events in the fetus/infant (e.g. large for gestational age infants, preterm delivery, preeclampsia, neonatal hypoglycemia),” she said.
Currently the FDA uses a five category rating to describe the safety profile of drugs used during pregnancy. (The FDA is considering revising this lettered system, as it is often being used to infer that the level of risk increases as the letter designation advances, which is not the intent according to the agency.)
In each category the risk of the drug needs to be weighed against the benefit of using it. Levemir® formally a category C drug has been moved to category B the same as NPH.
Here is a category breakdown:
A.) No risk to the fetus in any trimester
B.) Well controlled studies have failed to demonstrate risk to the fetus despite findings to the contrary in animal studies or animal studies show no risk and human studies are lacking.
C.) Risk can’t be ruled out. There isn’t sufficient evidence yet one way or another but adequate human studies do not exist. The benefit of using the drug may outweigh its risks.
D.) Positive evidence of risk to the fetus. Again, there may be instances when the use of the drug is acceptable such as in a life threatening situation. –
X.) Contraindicated in Pregnancy- studies have demonstrated fetal abnormalities or risk. Risks outweigh all benefits