What is the best approach for a 7-month pregnant woman with gestational diabetes mellitus (GDM) and hyperglycemia, currently on metformin (biguanide) 250mg twice daily, planning to add glargine (insulin glargine) in the morning and Actrapid (regular human insulin) pre-meals?

Insulin Regimen for Gestational Diabetes at 7 Months Pregnancy

Direct Recommendation

Insulin glargine should be administered once daily at bedtime (not morning) combined with Actrapid (regular insulin) before each meal, as this timing better addresses the fasting hyperglycemia characteristic of gestational diabetes while the prandial insulin covers postprandial excursions. 1, 2

Why Bedtime Dosing for Glargine is Preferred

• Glargine should be given at the same time each day, but bedtime administration is physiologically superior because it provides basal coverage overnight when hepatic gluconeogenesis is most active, directly targeting the elevated fasting glucose that is the hallmark of inadequate glycemic control in GDM 2

• The FDA label specifies glargine can be given "at any time of day but at the same time every day," but does not recommend morning dosing specifically 2

• Morning dosing of basal insulin may leave overnight periods with inadequate basal coverage, resulting in elevated fasting glucose 1

Insulin Initiation Strategy

Start with a 40% basal / 60% prandial distribution of total daily insulin dose:

• Calculate total daily insulin requirement as approximately 0.2 units/kg of current body weight 2
• Distribute 40% as glargine (bedtime) and 60% divided among three pre-meal Actrapid doses 1
• For a 70kg woman: Total ~14 units daily = 6 units glargine bedtime + 8 units Actrapid divided as 3-3-2 units before breakfast-lunch-dinner 1

Critical Glycemic Targets

Monitor fasting and postprandial glucose 4 times daily with strict targets:

• Fasting <95 mg/dL (5.3 mmol/L) 3, 1, 4
• 1-hour postprandial <140 mg/dL (7.8 mmol/L) OR 3, 1, 4
• 2-hour postprandial <120 mg/dL (6.7 mmol/L) 3, 1, 4

Titration Protocol

Adjust insulin doses every 3-4 days based on glucose patterns:

• If fasting glucose remains ≥95 mg/dL: Increase bedtime glargine by 2-4 units 1, 2
• If specific postprandial values exceed targets: Increase corresponding pre-meal Actrapid by 1-2 units 1
• Continue metformin 250mg twice daily as adjunctive therapy, though note this dose is subtherapeutic and insulin will be the primary agent 3, 4

Important Caveats About Metformin

The current metformin dose (250mg twice daily) is inadequate and should not be relied upon:

• Metformin crosses the placenta with umbilical cord levels equal to or higher than maternal levels 3
• Long-term offspring data from the MiG TOFU study showed 9-year-old children exposed to metformin had higher BMI, waist circumference, and waist-to-height ratios compared to insulin-exposed children 3
• The Endocrine Society recommends avoiding metformin as first-line therapy due to inferior outcomes compared to insulin 4
• Consider discontinuing metformin and relying solely on insulin given the concerning long-term metabolic effects on offspring 3, 4

Monitoring Requirements

Self-monitor blood glucose 4 times daily:

• Fasting (upon waking) 1, 4
• 1-hour after breakfast, lunch, and dinner 1, 4
• Check urine ketones if fasting glucose >200 mg/dL or with symptoms, as pregnancy is ketogenic and DKA can occur at lower glucose thresholds 1

Common Pitfalls to Avoid

• Do NOT mix or dilute glargine with any other insulin - it must be administered as a separate injection 2
• Do NOT administer glargine intravenously or via insulin pump - subcutaneous administration only 2
• Rotate injection sites within the same anatomical region (abdomen, thigh, or deltoid) to prevent lipodystrophy 2
• Do NOT reduce carbohydrate intake below 175g/day as this may compromise fetal growth 4

Why Insulin is Mandatory at This Stage

At 7 months gestation with inadequate control on metformin alone, insulin is non-negotiable:

• Insulin does not cross the placenta to any measurable extent, unlike oral agents 3, 4
• The American College of Obstetricians and Gynecologists designates insulin as the preferred first-line pharmacologic agent when medical nutrition therapy fails 1, 4
• No specific insulin regimen has demonstrated superiority, but the basal-bolus approach addresses both fasting and postprandial hyperglycemia characteristic of GDM 3, 1

Labor and Delivery Planning

Transition to intravenous insulin during active labor or cesarean section:

• Discontinue subcutaneous insulin and switch to IV insulin infusion during labor 1
• Stop all insulin immediately after delivery 1
• Monitor blood glucose before meals and 2 hours postprandially for 48 hours postpartum 1