A Look into how insulin detemir causes an increased risk of malformations and even death for neonates with mothers who are insulin dependent.
Chances of adverse maternal and fetal outcomes are increased when mothers have diabetes and even higher if the patient has uncontrolled diabetes. The increased adverse effects can include pregnancy-induced hypertension, low birth weight, and preterm labor, to name a few that are most studied. When gestational glucose metabolism is abnormal, these risks can become markedly dangerous to the mother and fetus. Long-acting insulins such as insulin detemir, insulin glargine, and insulin degludec reach the bloodstream several hours after injection and are known to lower glucose levels up to 24 hours after injection. These characteristics provide a steady background control of blood glucose levels over a long period and help optimize blood glucose levels with minimal risk of hypoglycemia. Due to the efficacious profile of these basal insulins, they are widely used to treat pregnant women with diabetes. Still, data remains limited on their risk of congenital disabilities or perinatal or neonatal death in a real-world setting. Therefore, the evaluation of Levemir in pregnancy study, also known as the EVOLVE study, was done to assess the effects of detemir compared with other long-acting insulins on the risk of severe birth outcomes in women with pre-existing diabetes in a real-world setting. A randomized control trial investigated the use of detemir versus NPH insulin in combination with insulin aspart in pregnant women with type one diabetes only. Other studies only assessed adverse maternal and neonatal outcomes in pregnant women with abnormal glucose metabolism; they did not compare the different basal long-acting insulins and their affect congenital malformations.
Optimal management of diabetes is of utmost importance in pregnant women. The goal is to decrease maternal hyperglycemia while decreasing the chances of hypoglycemic events, which prevents dangerous complications during pregnancy. The objective of the EVOLVE study was to evaluate the risk of major congenital malformations or perinatal or neonatal death when using detemir versus using other basal insulins like glargine in pregnant women with pre-existing diabetes. The study also investigated other endpoints such as HbA1c levels during pregnancy and the incidence of significant hypoglycemia and preeclampsia. The evolve study was a large multinational prospective noninterventional multicenter study done in pregnant women were pre-existing type one or type 2 diabetes. The study enrolled women in their early pregnancy stages at 92 facilities in 17 countries, including Europe, Israel, and Malaysia. Standard routine visits were conducted throughout the pregnancy up until delivery, and a one-month follow-up was done after delivery, followed by an additional one-year follow-up. Inclusion criteria included a positive pregnancy test with a gestational age of = 16 weeks at enrollment, type 1 or type 2 diabetes diagnosed before conception, treatment at the time of enrollment with detemir or other injectable antidiabetic treatments, and an unchanged treatment regimen for at least four weeks before conception. The primary endpoint was a composite of the proportion of pregnancies completing greater >/=22 weeks of gestation in women treated with detemir versus the other basal insulins. Maternal endpoints included HbA1c levels, and safety endpoints included significant hypoglycemia in preeclampsia during pregnancy.
Two thousand three hundred seventy-three women met the inclusion criteria 1457 were receiving basal insulin before enrollment. Seven hundred twenty-seven women were using insulin detemir, and 730 women were using another source of basal insulin therapy. There were 713 single baby pregnancies and 14 twin pairs in the detemir subgroup and 718 single pregnancies and 11 twin pairs in the “other” basal insulin subgroup. There was a total of 1481 fetuses born >=22 gestational weeks. Liveborn babies were 1345, and stillbirths totaled 15, with 3 in the detemir subgroup and 12 in the “other” insulin subgroup. Crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first and second trimester and a lower prevalence of major hypoglycemia, preeclampsia, and stillbirth with detemir vs. other basal insulin therapies pre-adjustment, and no significant differences post adjustment.
It can be concluded that insulin detemir is not inferior when compared to other basal insulin therapies in causing congenital malformations, perinatal or neonatal death, hypoglycemia, and stillbirth during pregnancies in pre-diagnosed diabetic women. The risk of using insulin detemir is comparable to the risk of using other basal insulin therapies. More extensive studies are needed to determine the risk of using insulin detemir during pregnancy vs. other basal insulin therapies. Studies such as this one are pivotal in creating guidelines on the best practices for pregnant women and their unborn fetuses when the patient has diabetes. Although this study didn’t warrant a change in recommendations, it’s a start to other studies that compare insulin therapy for pregnant women with diabetes.
- Optimal management of diabetes is of utmost importance in pregnant women. The goal is to decrease maternal hyperglycemia while limiting the chances of hypoglycemia, which prevents dangerous complications during pregnancy.
- Insulin detemir is not inferior when compared to other basal insulin therapies in causing congenital malformations, perinatal or neonatal death, hypoglycemia, and stillbirth during pregnancies in pre-diagnosed diabetic women.
- Larger studies are needed to determine the risk of using insulin detemir during pregnancy vs. other basal insulin therapies.
- Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study Elisabeth R.Mathiesen, Norsiah Ali, Alibegovic, Eleni Anastasiou, Katarzyna Cypryk, Harold de Valk, Jorge Dores, Fidelma Dunne, Mari-Anne Gall, Santiago Duran Garcia, Hélène P. Hanaire, Lise Lotte N. Husemoen, MarinaIvanišević, Hans-Peter Kempe, David R. McCance, Peter Damm Diabetes Care Sep 2021, 44 (9) 2069-2077; DOI: 10.2337/dc21-0472
- Li MF, Ma L, Yu TP, Zhu Y, Chen MY, Liu Y, Li LX. Adverse maternal and neonatal outcomes in pregnant women with abnormal glucose metabolism. Diabetes Res Clin Pract. 2020 Mar;161:108085. doi: 10.1016/j.diabres.2020.108085. Epub 2020 Feb 13. PMID: 32061817.
Erica Hicks, PharmD Candidate 2022, South College School of Pharmacy