What are the guidelines for using insulin degludec (insulin degludec) in pregnancy?

Insulin Degludec Use in Pregnancy

Insulin degludec is not specifically recommended for routine use during pregnancy, but can be considered in selected cases where benefits outweigh potential risks, particularly in patients with problematic hypoglycemia on other insulin regimens.

Current Guidelines on Insulin Use in Pregnancy

The American Diabetes Association (ADA) provides clear recommendations regarding insulin use during pregnancy:

• Insulin is the preferred agent for managing both type 1 and type 2 diabetes during pregnancy 1
• Either multiple daily injections or insulin pump technology can be used in pregnancy complicated by type 1 diabetes 1
• None of the currently available human insulin preparations have been demonstrated to cross the placenta 1
• Insulins studied in randomized controlled trials (RCTs) are preferred over those studied in cohort studies, which are preferred over those studied in case reports only 1

Insulin Degludec in Pregnancy: Evidence and Safety

The FDA label for insulin degludec states:

• Available data from one unpublished trial and published literature have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes 2
• In a randomized, open-label actively controlled clinical trial with 91 pregnant women with type 1 diabetes who received insulin degludec once daily, no clear evidence of maternal or fetal risk was observed 2
• Animal reproduction studies showed pre-and post-implantation losses and visceral/skeletal abnormalities in rats at doses 5 times the human exposure, similar to effects observed with human insulin (NPH) 2

Recent evidence from the EXPECT trial (2023) demonstrated:

• Insulin degludec was non-inferior to insulin detemir for glycemic control in pregnant women with type 1 diabetes 3
• No additional safety issues were observed with degludec compared to detemir 3

Clinical Decision Algorithm for Insulin Degludec in Pregnancy

1. First-line options:

   • Use insulin analogs with more established safety profiles in pregnancy (insulin aspart, lispro, detemir) 1, 4

2. Consider insulin degludec when:

   • Patient experiences problematic hypoglycemia on first-line insulin options 5
   • Wide glycemic variability persists despite optimization of other insulin regimens 5
   • Patient was well-controlled on degludec before pregnancy and switching may worsen control 6

3. Monitoring requirements if using degludec:

   • Regular blood glucose monitoring (fasting, preprandial, and postprandial)
   • Consider continuous glucose monitoring if indicated 7
   • Target fasting glucose <95 mg/dL, 1-hour postprandial <140 mg/dL, and 2-hour postprandial <120 mg/dL 7

Important Considerations and Pitfalls

• Insulin requirements change throughout pregnancy, requiring frequent titration to match changing requirements 1, 7
• Insulin resistance drops rapidly with delivery of the placenta, necessitating prompt dose adjustment postpartum 1
• Pregnant individuals with diabetes have an increased risk of hypoglycemia in the first trimester and altered counter-regulatory responses 1
• Education about prevention, recognition, and treatment of hypoglycemia is essential before, during, and after pregnancy 1

Case Experience

Small case series have reported successful outcomes with insulin degludec during pregnancy:

• No congenital neonatal malformations were observed in six reported cases 6
• Some cases showed improvement in glycemic control and reduction in glycemic variability 5
• However, these are limited by small sample sizes and retrospective nature 6, 5

Conclusion for Clinical Practice

While insulin degludec is not specifically approved as first-line therapy in pregnancy, recent evidence suggests it may be non-inferior to insulin detemir. For patients with problematic hypoglycemia or significant glycemic variability on other insulin regimens, degludec may be a reasonable alternative after discussing potential risks and benefits. The decision should be made in consultation with specialists experienced in managing diabetes in pregnancy.