Which insulin is safe during pregnancy?

From the Guidelines

Insulin is the preferred agent for managing diabetes in pregnancy, with human insulin and insulin analogs such as insulin lispro, insulin aspart, and insulin detemir being safe options. The most recent guidelines from 2023 recommend the use of insulin for managing type 1 and type 2 diabetes in pregnancy 1. According to these guidelines, insulin does not cross the placenta in significant amounts, making it safe for the developing fetus.

Key Considerations

• Insulin requirements typically increase during pregnancy, especially in the second and third trimesters, due to increasing insulin resistance caused by placental hormones 1.
• Close monitoring of blood glucose levels and regular adjustment of insulin doses under medical supervision is essential for managing diabetes during pregnancy 1.
• The physiology of pregnancy necessitates frequent titration of insulin to match changing requirements, and referral to a specialized center offering team-based care is recommended if available 1.

Insulin Options

• Human insulin has been used for decades and has a well-established safety profile 1.
• Among the rapid-acting analogs, insulin lispro and insulin aspart are preferred options as they have been extensively studied in pregnant women 1.
• For long-acting insulins, insulin detemir is often recommended, and NPH insulin is also commonly used as an intermediate-acting option during pregnancy 1.

Management

• Either multiple daily injections or insulin pump technology can be used in pregnancy complicated by type 1 diabetes 1.
• Education for people with diabetes and family members about the prevention, recognition, and treatment of hypoglycemia is important before, during, and after pregnancy to help prevent and manage hypoglycemia’s risks 1.

From the FDA Drug Label

8 USE IN SPECIFIC POPULATIONS

1. 1 Pregnancy Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes insulin 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 in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking HUMALOG Although there are limited clinical studies of the use of HUMALOG in pregnancy, published studies with human insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and during pregnancy improves fetal outcome In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0. 8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1,0.25, and 0.75 unit/kg/day (0.03,0.08, and 0. 24 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.

Insulin Lispro is classified as Pregnancy Category B, which means that animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

• The FDA label states that insulin lispro has been shown to have no adverse effects on female fertility, implantation, or fetal viability and morphology in animal studies.
• However, fetal growth retardation was observed at higher doses in rats.
• The label also notes that published studies with human insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and during pregnancy improves fetal outcome.
• Therefore, insulin lispro may be considered safe during pregnancy when used under the guidance of a healthcare provider and with careful monitoring of glucose control 2.

8 USE IN SPECIFIC POPULATIONS 8. 1 Pregnancy Risk Summary Available information from published randomized controlled trials with insulin aspart products use during the second trimester of pregnancy have not reported an association with insulin aspart products and major birth defects or adverse maternal or fetal outcomes

Insulin Aspart has also been studied in pregnancy, and the FDA label states that:

• Available information from published randomized controlled trials has not reported an association with insulin aspart products and major birth defects or adverse maternal or fetal outcomes.
• Animal reproduction studies have not shown any adverse effects on fetal development at doses up to 8 times the human dose.
• Therefore, insulin aspart may also be considered safe during pregnancy when used under the guidance of a healthcare provider and with careful monitoring of glucose control 3.

From the Research

Insulin Safety During Pregnancy

• Insulins lispro, aspart, and detemir are considered safe for use in pregnant women with type 1 diabetes 4, 5.
• Insulin glargine use in pregnancy has shown no major safety concerns, although most studies are small and retrospective 4, 5, 6.
• Insulin glulisine and degludec have not been studied in pregnancy, and their use is not recommended 4, 5.
• The use of insulin analogues in pregnancy may improve post-prandial glycaemic control and reduce the risk of hypoglycaemia compared to human insulin 4, 5.

Specific Insulin Types

• Insulin lispro and insulin aspart are safe in pregnancy and may be used to improve glycaemic control in women with type 1 diabetes 4, 5.
• Insulin detemir has been shown to improve fasting plasma glucose without increasing the incidence of hypoglycaemia in women with type 1 diabetes 5.
• Insulin glargine can be continued safely during pregnancy in women who are already taking it prior to pregnancy and have achieved good glycemic control with it 6.

Comparison with Human Insulin

• Insulin analogues are viable therapeutic options for diabetes in pregnancy, with safety and efficacy comparable to human insulin 4, 5.
• The evidence analyzed to date has a moderate-to-high risk of bias and does not allow the conclusion that insulin analogs are more effective when compared with human insulin to treat diabetic pregnant women 7.