Is it safe to use Ryzodeg (insulin degludec/insulin aspart) during pregnancy in a woman with type 1 or type 2 diabetes, and how should it be managed?

Ryzodeg Should Not Be Used During Pregnancy

Ryzodeg (insulin degludec/insulin aspart) is not recommended for use during pregnancy and should be switched to standard insulin regimens that have established safety profiles in pregnancy, such as NPH insulin or rapid-acting insulin analogs (aspart, lispro) in basal-bolus regimens. 1

Why Ryzodeg Is Not Recommended

The 2025 ADA Standards of Care explicitly state that insulin should be used to manage type 1 diabetes in pregnancy and is preferred for type 2 diabetes and gestational diabetes 1. However, the guideline emphasizes using insulin regimens with established pregnancy safety data. Ryzodeg contains insulin degludec, an ultra-long-acting basal insulin that lacks sufficient safety data in pregnancy.

The 2025 Endocrine Society/European Society of Endocrinology joint guideline reinforces that insulin is the preferred antidiabetic medication in pregnancy 2, but this refers to insulin preparations with documented safety profiles in pregnancy—not newer formulations like degludec.

Limited Real-World Data

While there is one small observational study showing that 67 women with type 1 diabetes who used insulin degludec throughout pregnancy had similar outcomes to those using other long-acting insulins 3, this single study is insufficient to establish safety. The study found no increased malformations or pregnancy complications, but the sample size is too small to detect rare adverse events, and it was not a randomized controlled trial.

Two case reports of women who continued degludec during the first trimester showed no malformations but both infants required NICU admission for hypoglycemia 4. This raises concerns about neonatal complications even when maternal outcomes appear acceptable.

What to Use Instead

Switch to a basal-bolus regimen using:

• NPH insulin for basal coverage (the most extensively studied basal insulin in pregnancy)
• Rapid-acting insulin analogs (aspart, lispro) for mealtime coverage

Alternatively, consider automated insulin delivery (AID) systems with continuous glucose monitoring, which have been studied in pregnancy and show improved nocturnal time-in-range and reduced hypoglycemia compared to standard care 1.

Practical Management

If a patient presents already pregnant on Ryzodeg:

1. Switch immediately to NPH insulin twice daily or insulin detemir (which has more pregnancy data than degludec)
2. Add rapid-acting insulin (aspart or lispro) before meals
3. Implement frequent glucose monitoring (ideally CGM with pregnancy-specific targets)
4. Titrate insulin frequently as requirements change throughout pregnancy—insulin needs typically increase progressively until the third trimester, then may plateau 1

Key pregnancy-specific glucose targets:

• Fasting: <95 mg/dL
• 1-hour postprandial: <140 mg/dL
• 2-hour postprandial: <120 mg/dL

Critical Pitfall to Avoid

Do not continue Ryzodeg simply because a patient has good glycemic control on it pre-pregnancy. The lack of adequate safety data in pregnancy outweighs the convenience of fewer injections. Pregnancy is not the time to use medications without established safety profiles when effective alternatives exist.

A rapid drop in insulin requirements in late third trimester may indicate placental insufficiency 1—monitor closely and consider fetal surveillance if this occurs.