What is the best management plan for a pregnant diabetic patient with a history of hyperglycemia, currently on metformin (biguanide) and semaglutide (glucagon-like peptide-1 receptor agonist), who requires a medication change due to pregnancy?

Management of Diabetes in Pregnancy with Confirmed Pregnancy

You are correct—discontinue semaglutide immediately and transition to insulin therapy, as GLP-1 receptor agonists like semaglutide are not approved for use in pregnancy and lack safety data for fetal outcomes. 1, 2

Immediate Medication Changes

Discontinue Semaglutide

• Semaglutide must be stopped immediately upon pregnancy confirmation, as no GLP-1 receptor agonists are FDA-approved or recommended for use during pregnancy 1, 2
• There are no adequate studies on fetal safety with semaglutide exposure during pregnancy 2, 3

Metformin Decision

• Continue metformin during pregnancy if the patient has been adherent, as it can be used as adjunctive therapy to insulin for type 2 diabetes in pregnancy 1
• However, given her apparent non-adherence (last fill in a previous month with remaining refills), address barriers to medication adherence before relying on metformin 1
• Metformin crosses the placenta and should not be used if she develops hypertension, preeclampsia, or risk factors for intrauterine growth restriction 1
• If metformin is continued, counsel that it may reduce maternal weight gain and macrosomia risk, but doubles the risk of small-for-gestational-age neonates 1

Insulin Initiation Strategy

Preferred Insulin Regimen

• Start a basal-bolus insulin regimen with human insulin preparations (NPH for basal, regular or rapid-acting analogs for prandial coverage) 1, 4
• Insulin is the only FDA-approved medication for diabetes in pregnancy and does not cross the placenta 1, 2, 5
• Both multiple daily injections and insulin pump therapy are acceptable, with neither proven superior 1

Initial Dosing Calculations

• Calculate total daily insulin dose (TDD) based on current weight and trimester:
  • First trimester: 0.7-0.8 units/kg/day
  • Second trimester: 0.8-1.0 units/kg/day
  • Third trimester: 0.9-1.2 units/kg/day 4, 5
• Distribute as 40-50% basal insulin and 50-60% prandial insulin (divided among three meals based on carbohydrate content) 4, 5
• Given her HbA1c and apparent poor control, start at the higher end of dosing ranges 4, 5

Insulin Titration Plan

• Expect weekly or biweekly dose increases during the second trimester as insulin resistance rapidly increases from placental hormones 4, 5
• Insulin requirements typically double by the third trimester compared to prepregnancy needs 6, 5
• Adjust basal insulin based on fasting glucose and prandial insulin based on postprandial values 4, 5

Glycemic Targets for Pregnancy

Self-Monitoring Blood Glucose Goals

• Fasting glucose: <95 mg/dL 1, 4
• 1-hour postprandial: <140 mg/dL 1, 4
• 2-hour postprandial: <120 mg/dL 1, 4
• Monitor fasting and postprandial glucose 4-7 times daily 1, 6

HbA1c Targets

• Target HbA1c <6% if achievable without hypoglycemia 1, 4
• Check HbA1c monthly due to altered red blood cell kinetics in pregnancy 4, 6
• Use HbA1c as a secondary measure alongside self-monitoring, as it may not capture real-time glycemic excursions 4, 6

Specialist Referral

Maternal-Fetal Medicine and Endocrinology

• Referral to a specialized center with team-based care is strongly recommended given the complexity of insulin management in pregnancy 1, 4
• The team should include maternal-fetal medicine specialist, endocrinologist experienced in pregnancy diabetes, registered dietitian nutritionist, diabetes care and education specialist, and social worker 1
• Specialized care improves outcomes through frequent insulin titration, nutritional counseling, and close fetal monitoring 1, 4

Additional Pregnancy-Specific Management

Preconception Optimization (Retroactive Counseling)

• Review and discontinue all potentially teratogenic medications including ACE inhibitors, ARBs, and statins if she was taking any 1
• Start low-dose aspirin (81 mg daily) by end of first trimester to reduce preeclampsia risk 1

Hypoglycemia Prevention

• Educate patient and family on hypoglycemia recognition and treatment, as pregnancy increases hypoglycemia risk, especially in the first trimester 1, 5
• Insulin resistance drops dramatically immediately postpartum, requiring dose reduction to roughly 50% of end-pregnancy requirements 1, 6
• Lactation increases overnight hypoglycemia risk, requiring further insulin adjustments postpartum 1

Diabetic Ketoacidosis Risk

• Provide ketone strips for home testing, as pregnancy is a ketogenic state and DKA can occur at lower glucose levels than in non-pregnant individuals 1
• Educate on DKA prevention and when to seek emergency care 1

Critical Pitfalls to Avoid

• Do not use fixed insulin doses—pregnancy physiology demands frequent adjustments, particularly during the second trimester when insulin resistance increases rapidly 4, 6
• Do not rely solely on HbA1c for insulin adjustment decisions, as self-monitoring provides more actionable real-time data 4, 6
• Do not continue semaglutide under any circumstances during pregnancy due to lack of safety data 1, 2
• Do not use glyburide as it crosses the placenta (70% of maternal levels in cord blood) and is associated with increased neonatal hypoglycemia and macrosomia 1, 7
• Address medication adherence barriers before assuming metformin will provide adequate adjunctive control 1

Postpartum Planning

Immediate Postpartum Care

• Reduce insulin to 50% of end-pregnancy doses or 80% of prepregnancy doses immediately after delivery 6
• Monitor closely for hypoglycemia, especially during breastfeeding with erratic sleep and eating schedules 1, 6

Long-Term Follow-Up

• Screen for persistent diabetes at 4-12 weeks postpartum with 75-gram oral glucose tolerance test using non-pregnancy diagnostic criteria 1
• Continue diabetes screening every 1-3 years lifelong, as she has 50-70% risk of developing type 2 diabetes over 15-25 years 1
• Encourage breastfeeding, which reduces maternal risk of type 2 diabetes and provides metabolic benefits to offspring 1, 6
• Implement effective contraception until glycemic control is optimized for any future pregnancies 1