What are the approved long-acting and short-acting insulins for use in pregnancy complicated by diabetes?

Approved Insulins for Pregnancy Complicated by Diabetes

For pregnancy complicated by diabetes, the FDA-approved and guideline-recommended insulins include: SHORT-ACTING: insulin lispro and insulin aspart (both FDA Category B); LONG-ACTING: insulin detemir (FDA Category B) and NPH insulin, with insulin glargine considered acceptable despite limited data. 1, 2, 3

Short-Acting Insulin Analogues (Preferred)

Insulin lispro and insulin aspart are FDA Category B medications that have been reclassified from Category C based on safety data in pregnant women with type 1 diabetes. 2, 3

• Both analogues are safe and effective for managing postprandial glucose control in pregnancy complicated by type 1 and type 2 diabetes. 4, 5
• These rapid-acting analogues improve postprandial glycemic control compared to regular human insulin and are considered first-line options. 4, 5
• Regular human insulin remains an acceptable alternative if a woman is well-controlled on it pre-pregnancy, as there is no imperative to switch if glycemic targets are being met. 5

Not Recommended Short-Acting Analogues

• Insulin glulisine has no published data in pregnancy and cannot be recommended. 5, 2

Long-Acting Insulin Analogues

First-Line Long-Acting Option

Insulin detemir is FDA Category B and has the strongest evidence base as the preferred long-acting analogue in pregnancy. 5, 2, 3

• Head-to-head comparison with NPH insulin in type 1 diabetes showed improved fasting plasma glucose without increased hypoglycemia, though fetal outcomes were similar. 5
• The greater evidence base and hypoglycemia risk reduction support insulin detemir as first-line for long-acting coverage. 5, 3

Alternative Long-Acting Options

NPH (intermediate-acting) human insulin remains a safe and effective option throughout pregnancy. 5

• If a woman is well-controlled on NPH insulin pre-pregnancy, there is no strong need to switch to an analogue. 5
• NPH has decades of safety data and does not cross the placenta. 1

Insulin glargine can be continued if needed for glycemic control, despite limited prospective data. 5, 2

• Most studies are small and retrospective, but no major safety concerns have been reported. 5, 2, 3
• It is reasonable to continue glargine if required to achieve excellent glycemic control, particularly if switching would destabilize diabetes management. 5

Not Recommended Long-Acting Analogues

• Insulin degludec has not been studied in pregnancy and should be avoided. 2, 3

Critical Implementation Points

None of the currently available human insulin preparations cross the placenta, making them inherently safe for fetal exposure. 1

• Insulins studied in randomized controlled trials (lispro, aspart, detemir) are preferred over those studied only in cohort studies (glargine), which are preferred over those with only case reports. 1
• Both multiple daily injections and continuous subcutaneous insulin infusion are acceptable delivery strategies, with neither shown to be superior during pregnancy. 1

Common Pitfall to Avoid

Do not switch insulin types solely for the sake of using an analogue if a woman is well-controlled on human insulin (regular or NPH), as the lack of definitive fetal outcome benefits does not justify destabilizing glycemic control. 5

• The primary advantage of analogues is reduced hypoglycemia risk, which is most relevant in type 1 diabetes with frequent severe hypoglycemia. 1, 3
• For gestational diabetes or type 2 diabetes where hypoglycemia risk is lower, there is little justification for preferring long-acting analogues over NPH insulin. 5