Is isophane (NPH) insulin safe for use in pregnant patients with diabetes?

Safety of Isophane (NPH) Insulin in Pregnant Patients with Diabetes

Isophane (NPH) insulin is safe and effective for use in pregnant patients with diabetes and is considered a preferred insulin option during pregnancy. 1

Evidence Supporting NPH Insulin Use in Pregnancy

• None of the currently available human insulin preparations, including NPH insulin, have been demonstrated to cross the placenta, making them safe options for pregnant patients 1
• Insulin is the preferred agent for management of both type 1 and type 2 diabetes during pregnancy 1
• NPH insulin has an established safety profile in pregnancy, with no evidence of adverse fetal outcomes when used to achieve glycemic targets 2

Insulin Management During Pregnancy

Type 1 Diabetes

• Insulin should be used to manage type 1 diabetes in pregnancy without exception 1
• Either multiple daily injections (which may include NPH as basal insulin) or insulin pump technology can be used effectively 1
• Pregnant individuals with type 1 diabetes have an increased risk of hypoglycemia in the first trimester due to altered counter-regulatory responses 1

Type 2 Diabetes

• Insulin is the preferred treatment for type 2 diabetes in pregnancy 1
• NPH insulin can be used as part of a basal-bolus regimen or in combination with rapid-acting insulin 1
• An RCT of metformin added to insulin for type 2 diabetes showed fewer macrosomic neonates but doubled the risk of small-for-gestational-age neonates, highlighting the importance of insulin therapy 1

Physiological Considerations

• Early pregnancy is characterized by enhanced insulin sensitivity and lower glucose levels, which may require lower insulin doses 1
• Around 16 weeks, insulin resistance begins to increase, with total daily insulin doses increasing linearly (approximately 5% per week through week 36) 1
• This typically results in a doubling of daily insulin requirements compared to pre-pregnancy 1
• Insulin requirements level off toward the end of the third trimester and drop rapidly with delivery of the placenta 1

Clinical Considerations When Using NPH Insulin

• NPH insulin should be properly mixed before administration (turn the cartridge up and down at least 10 times until the liquid appears uniformly white and cloudy) 3
• The cloudy material in an insulin suspension will settle to the bottom of the cartridge, so the contents must be mixed before each injection 3
• Frequent blood glucose monitoring and insulin dose adjustments are necessary throughout pregnancy due to changing insulin requirements 1

Safety Considerations and Potential Adverse Effects

• Hypoglycemia risk is increased during pregnancy, particularly in the first trimester for those with type 1 diabetes 1, 3
• Local reactions may occur at injection sites, including redness, swelling, and itching 3
• Generalized insulin allergy occurs rarely but can cause serious reactions requiring emergency medical care 3

Glycemic Targets During Pregnancy

• Recommended glucose targets for pregnant women with diabetes:
  • Fasting glucose: 70–95 mg/dL (3.9–5.3 mmol/L) 1
  • One-hour postprandial glucose: 110–140 mg/dL (6.1–7.8 mmol/L) 1
  • Two-hour postprandial glucose: 100–120 mg/dL (5.6–6.7 mmol/L) 1
• A target A1C of <6% (42 mmol/mol) is optimal during pregnancy if it can be achieved without significant hypoglycemia 1

Comparison with Insulin Analogues

• While insulin analogues (both rapid-acting and long-acting) have been increasingly used in pregnancy, there is no strong evidence that they provide superior fetal outcomes compared to human insulins like NPH 2
• For women who are well-controlled on NPH insulin, there is no strong justification to switch to long-acting analogues 2
• The lack of definitive fetal benefits with insulin analogues compared to NPH insulin supports the continued use of NPH in pregnant women 2

Additional Management Considerations

• Pregnant individuals with type 1 or type 2 diabetes should be prescribed low-dose aspirin 100–150 mg/day starting at 12 to 16 weeks of gestation to lower the risk of preeclampsia 1
• Due to the complexity of insulin management in pregnancy, referral to a specialized center offering team-based care is recommended when available 1
• Education about hypoglycemia prevention, recognition, and treatment is essential for pregnant patients using insulin and their family members 1, 3