Glargine Safety During Pregnancy: What Expecting Mothers Should Know

Insulin glargine, a long-acting insulin analogue, is widely used by non-pregnant adults. However, there is limited research on its safety for pregnant women and their babies. While some studies indicate that insulin glargine does not cross the placenta and is safe for use during pregnancy, others suggest that it may increase fetal growth and other mitogenic effects. There is a need for more research, particularly randomised controlled trials, to establish the safety of insulin glargine during pregnancy conclusively.

Insulin glargine does not cross the placenta at therapeutic concentrations

Insulin glargine is a long-acting insulin analogue with greater stability and duration of action than regular human insulin. Its long duration of action and decreased incidence of hypoglycaemia provide potential advantages for its use during pregnancy. However, there is a lack of research on the placental pharmacokinetics of insulin glargine.

Trans-placental transfer studies have been conducted to address this gap in knowledge. These studies show that insulin glargine does not cross the placenta when used at therapeutic concentrations. In other words, when insulin glargine is used at typical doses, it is unlikely to enter the fetal circulation.

In trans-placental transfer studies, researchers obtained placentas from healthy pregnancies and set up independent maternal and fetal circulatory systems. Insulin glargine was then added to the maternal circulation at therapeutic concentrations of 150 pmol/l (20 μU/ml). The appearance of insulin glargine in the fetal circulation was analysed, and no detectable amount was found.

Additional experiments were carried out at insulin glargine concentrations 1,000 times higher than therapeutic levels (150, 225, and 300 nmol/l). Even at these extremely high concentrations, the rate of transfer to the fetal circulation remained low.

These findings suggest that the placenta has a wide capacity to block insulin glargine transfer to the fetal compartment. This is likely due to the placenta's ability to sequester and/or metabolise insulin glargine, even at concentrations far above therapeutic levels.

While there is no definitive evidence of adverse outcomes associated with insulin glargine use during pregnancy, more research is needed to establish it as a preferred basal insulin for managing hyperglycaemia during pregnancy.

Insulin glargine is not associated with adverse maternal or neonatal outcomes

Insulin glargine is a long-acting synthetic version of the insulin hormone that can help control blood sugar levels in adults and children with type 1 and type 2 diabetes. It is critical to maintain normal blood sugar levels during pregnancy. Insulin requirements may change during pregnancy, and doctors may adjust the type and dosage of insulin.

While insulin glargine has been widely used in non-pregnant adults, there is limited evidence regarding its safety in pregnant women. However, several studies and reviews indicate that insulin glargine does not increase the risk of adverse maternal or neonatal outcomes during pregnancy.

Firstly, trans-placental transfer studies show that insulin glargine, when used at therapeutic concentrations, does not cross the placenta. This suggests that it is unlikely to cause fetal harm. Secondly, case reports and observational studies (both prospective and retrospective) have found no association between the use of insulin glargine during pregnancy and adverse maternal or neonatal outcomes.

In one systematic review and meta-analysis, eight studies involving 702 women with pregestational or gestational diabetes who used either insulin glargine or NPH insulin during pregnancy were analysed. No statistically significant differences were found in the occurrence of fetal outcomes between the two groups. This suggests that insulin glargine does not increase the risk of adverse fetal outcomes compared to NPH insulin.

Additionally, a transplacental transfer study found that insulin glargine did not cross the placenta when used at therapeutic concentrations. Even at extremely high concentrations, the rate of transfer across the placenta remained low.

Despite these findings, it is important to note that there are currently no randomised controlled trials on the use of insulin glargine during pregnancy. Therefore, while the available evidence suggests that insulin glargine is safe for use during pregnancy, more research is needed to establish it as a preferred basal insulin for managing hyperglycemia in pregnancy.

Insulin glargine may be continued during pregnancy if good glycemic control is achieved

Insulin glargine, a long-acting insulin, is a popular synthetic version of the natural hormone insulin, which lowers blood sugar levels. It is used to improve blood sugar control in adults and children (from age 6) with type 1 and type 2 diabetes.

During pregnancy, it is crucial to maintain normal blood sugar levels. Insulin requirements may change during pregnancy, and doctors may adjust the type and dosage of insulin.

While insulin glargine has been available for almost two decades, it is not commonly prescribed to pregnant women. There is a lack of extensive clinical trials evaluating its safety for pregnant women and their developing fetuses. However, some studies have been conducted to address this question.

Placental Transfer Studies

Placental transfer studies have shown that insulin glargine, when used at therapeutic concentrations, does not cross the placenta. Even at concentrations 1,000 times higher than therapeutic levels, the transfer rate remained low.

Animal Studies

In animal studies, insulin glargine, when dosed at 50 and 10 times the human subcutaneous dose during organogenesis, did not show significantly different effects compared to regular human insulin in rats and rabbits. In rabbits, five fetuses from two high-dosed litters exhibited dilation of the cerebral ventricles, but fertility and early embryonic development appeared normal.

Human Studies

A systematic review and meta-analysis of eight studies involving 702 women with pregestational or gestational diabetes treated with either insulin glargine (n = 331) or NPH insulin (n = 371) found no statistically significant differences in fetal outcomes. There was no evidence of increased adverse fetal outcomes with the use of insulin glargine compared to NPH insulin.

Several case reports and observational studies (both prospective and retrospective) have also shown that the use of insulin glargine during pregnancy is not associated with any adverse maternal or neonatal outcomes.

Recommendations and Conclusions

Insulin glargine can be continued safely during pregnancy in women who are already taking it prior to pregnancy and have achieved good glycemic control. However, more evidence, preferably from randomized controlled trials or large prospective observational studies, is needed to establish it as the first-line or preferred basal insulin for managing hyperglycemia during pregnancy.

In summary, while insulin glargine appears safe to use during pregnancy for women with good glycemic control, further research is required to confirm its status as the preferred treatment option.

Insulin glargine may be safer than NPH insulin during pregnancy

Insulin glargine, a long-acting insulin, is considered safe for use during pregnancy by many organisations across the globe. However, it lacks randomised controlled trial evidence as a safe basal insulin during pregnancy.

Trans-placental transfer studies show that insulin glargine does not cross the placenta when used at therapeutic concentrations. In addition, its use during pregnancy is not associated with any adverse maternal or neonatal outcomes, as shown in many case reports and observational studies.

A review of eight studies reporting on a total of 702 women with pregestational or gestational diabetes treated with either insulin glargine or NPH insulin during pregnancy found no statistically significant differences in the occurrence of fetal outcomes. The review concluded that there was no evidence of increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to NPH insulin.

Another study found that insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta, suggesting that the placenta is able to block the transfer of insulin glargine to the fetal compartment.

While insulin glargine may be safer than NPH insulin during pregnancy, it is important to note that there are no controlled data in human pregnancy, and more evidence is needed before recommending it as the preferred basal insulin during pregnancy. Poorly controlled diabetes during pregnancy increases the risk of adverse outcomes for both the mother and the fetus. Therefore, careful monitoring of glucose control is essential.

Insulin requirements may change during pregnancy

Insulin glargine requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential.

Trans-placental transfer studies show that insulin glargine does not cross the placenta when used at therapeutic concentrations. However, at concentrations 1,000 times higher than therapeutic levels, there was a detectable accumulation of insulin glargine in the fetal circuit. 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.

There is a lack of randomised controlled trial evidence for the safety of insulin glargine during pregnancy. However, its use during pregnancy is not associated with any adverse maternal or neonatal outcomes as shown in many case reports and observational studies (both prospective and retrospective). It is considered safe by many organisations globally.

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