Use of Insulin Glargine in Pregnancy
Insulin glargine can be safely used during pregnancy, though it was historically classified as pregnancy category C; however, current FDA labeling and accumulating clinical evidence show no clear association with adverse developmental outcomes, making it an acceptable basal insulin option for pregnant women with diabetes. 1
FDA Labeling and Safety Data
The FDA label for insulin glargine states that published studies have not reported a clear association between insulin glargine use during pregnancy and adverse developmental outcomes, major birth defects, miscarriage, or adverse maternal or fetal outcomes. 1 However, the label acknowledges that these studies cannot definitively establish the absence of risk due to methodological limitations including small sample sizes and some lacking comparator groups. 1
Animal reproduction studies in rats and rabbits at doses 50 times and 10 times the human dose, respectively, showed effects that did not generally differ from regular human insulin. 1
Guideline Recommendations
The American Diabetes Association guidelines from 2015 note that all insulins are pregnancy category B except for glargine and glulisine, which are labeled category C. 2 However, this classification system has since been replaced, and more recent evidence supports its use.
The 2024 ADA guidelines emphasize that insulin is the preferred agent for management of type 1 and type 2 diabetes in pregnancy, with both multiple daily injections and insulin pump technology being reasonable delivery strategies. 2
Clinical Evidence Supporting Safety
Multiple observational studies demonstrate the safety of insulin glargine in pregnancy:
A retrospective multicenter study of 107 Type 1 diabetic pregnancies using insulin glargine showed a congenital malformation rate of 4.9%, which is within the expected range for diabetic pregnancies treated with traditional insulins. 3
A case-control study of 100 Type 1 diabetic pregnancies found comparable glycemic control between insulin glargine and NPH insulin, with no adverse effects associated with glargine use at conception or during pregnancy. 4
A 2009 review of approximately 335 pregnancies with Type 1 diabetes using insulin glargine showed an incidence of congenital malformation similar to that obtained with human insulin. 5
Practical Considerations for Use
Women already taking insulin glargine prior to pregnancy who have achieved good glycemic control can safely continue it throughout pregnancy. 6 This approach avoids disrupting established glycemic control during a critical period.
Glycemic Targets During Pregnancy
When using insulin glargine, aim for the following targets:
- Fasting glucose: 70-95 mg/dL 7
- One-hour postprandial: 110-140 mg/dL 7
- Two-hour postprandial: 100-120 mg/dL 7
- A1C: <6% if achievable without significant hypoglycemia 2, 7
Insulin Dosing Adjustments
Insulin requirements change dramatically throughout pregnancy:
- First trimester: Insulin requirements often decrease due to enhanced insulin sensitivity; hypoglycemia risk increases, particularly in Type 1 diabetes. 7, 8
- Second trimester: Insulin resistance increases exponentially, requiring weekly or biweekly dose increases starting around 16 weeks. 7, 8
- Third trimester: Requirements typically double compared to pre-pregnancy but level off toward the end. 7, 8
- Postpartum: Insulin requirements drop rapidly with placental delivery. 7, 8
Important Caveats and Clinical Pitfalls
A common pitfall is switching from insulin glargine to NPH insulin solely based on outdated pregnancy category classifications, which may disrupt established glycemic control. The evidence does not support mandatory switching in women with good control on glargine. 3, 4
Hypoglycemia Risk
Pregnant individuals with Type 1 diabetes have altered counter-regulatory responses that may decrease hypoglycemia awareness. 2 Education about hypoglycemia prevention, recognition, and treatment is essential for patients and family members. 7, 8
Additional Management Requirements
- Frequent blood glucose monitoring and insulin dose adjustments are necessary throughout pregnancy. 7
- Referral to a specialized center offering team-based care is recommended when available. 7, 8
- Low-dose aspirin (100-150 mg/day) should be prescribed starting at 12-16 weeks gestation to reduce preeclampsia risk. 7, 8
Comparison with NPH Insulin
While NPH insulin remains a well-established safe option in pregnancy 7, insulin glargine offers potential advantages including:
- Better fasting and post-breakfast glycemic values in some studies 9
- 24-hour peakless action profile that may reduce nocturnal hypoglycemia 4
- Comparable overall glycemic control to NPH 4
One study raised concern about higher frequency of femoral length <50th centile with glargine use 9, but this finding has not been replicated in other studies and requires further investigation.