Insulin analogues in pregnancy and specific congenital anomalies: a literature review

Abstract

SummaryInsulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

Insulin Autoantibody-Related Hypoglycemic Coma in a Pregnant Woman with Type 1 Diabetes Mellitus

“…There is no data regarding insulin aspart and occurrence of autoimmune hypoglycemia. On the contrary, another short-acting insulin glulisine has been reported to cause autoimmune hypoglycemia [16] besides, the safety profile of insulin glulisine in pregnancy is still unknown [17]. Finally, insulin glargine has a longer duration of action as compared with insulin detemir, so we switched the basal insulin to insulin glargine to help maintain a more stable baseline glycemic status [8].…”

Gestational Diabetes Mellitus:current knowledge and unmet needs

“…A review by Lambert and Holt on the use of insulin analogs in pregnancy showed that compared with RI, the use of aspart and lispro is associated with better maternal glycemic control and a similar fetal outcome. No evidence of increased risk of congenital anomalies has been reported . Because insulin aspart and lispro are licensed for use during pregnancy in Europe, both insulin lispro and insulin aspart can be safely administered in pregnancy.…”

“…The data on insulin glargine in pregnancy appear to be insufficient because most of the studies that have included this drug are small and retrospective . Furthermore, insulin glargine has insulin‐like growth factor (IGF)‐1‐binding properties, which could be a disadvantage in pregnancy . However, as for RI, insulin glargine does not to cross the placental barrier .…”

“…No evidence of increased risk of congenital anomalies has been reported. 63 Because insulin aspart and lispro are licensed for use during pregnancy in Europe, both insulin lispro and insulin aspart can be safely administered in pregnancy.…”

“…62 Furthermore, insulin glargine has insulin-like growth factor (IGF)-1-binding properties, which could be a disadvantage in pregnancy. 63,67 However, as for RI, insulin glargine does not to cross the placental barrier. 68 There is no evidence to support the use of insulin glargine in GDM.…”