What are the recommended doses of insulin and metformin for a pregnant woman with gestational diabetes or overt diabetes?

Insulin and Metformin Dosing in Pregnancy

Insulin is the preferred medication for managing diabetes in pregnancy, with no specific starting dose universally recommended—dosing must be titrated frequently based on blood glucose monitoring, typically requiring 2-3 times the pre-pregnancy dose by the third trimester. 1, 2 Metformin is not recommended as first-line therapy in pregnancy, but when used (typically 500-2550 mg/day in divided doses per FDA labeling), it should only be considered after insulin or when insulin is refused. 3, 4

Insulin Dosing Strategy

Initial Dosing and Titration Approach

• No standardized starting dose exists—insulin requirements are highly individualized and change dramatically throughout pregnancy 2, 5
• For insulin-naïve patients with type 2 diabetes, consider starting at 0.1-0.2 units/kg once daily in the evening or 10 units once or twice daily, then adjust to achieve glycemic targets 6
• Basal-bolus regimens (combination of long-acting and short-acting insulin) are most commonly used, with a smaller proportion as basal insulin and greater proportion as prandial insulin 1, 2

Pregnancy-Specific Insulin Requirement Changes

• First trimester: Insulin requirements often decrease due to enhanced insulin sensitivity, increasing hypoglycemia risk 2, 7
• Second trimester (after 16 weeks): Requirements increase almost linearly and most dramatically, with weekly or biweekly dose increases needed 1, 2, 7
• Third trimester: Total daily insulin typically doubles to triples compared to pre-pregnancy doses, with requirements plateauing around 30 weeks gestation 2, 8, 7
• Post-delivery: Insulin resistance drops precipitously after placental delivery—resume at either 80% of pre-pregnancy doses or 50% of end-of-pregnancy doses 2, 7

Monitoring Requirements for Dose Adjustment

• Check blood glucose 4-6 times daily: fasting upon waking and after each main meal 2, 3
• Target glucose levels: fasting 70-95 mg/dL, 1-hour postprandial 110-140 mg/dL, 2-hour postprandial 100-120 mg/dL 2, 3
• Evaluate and adjust insulin requirements every 2-3 weeks as pregnancy progresses 2
• Critical warning: A rapid reduction in insulin requirements may indicate placental insufficiency and requires immediate medical evaluation 2

Delivery Methods

• Both multiple daily injections and continuous subcutaneous insulin infusion (pump) are acceptable—neither is superior 1, 2
• Human insulin preparations that do not cross the placenta are preferred 2

Metformin Dosing (When Used)

FDA-Approved Dosing (Non-Pregnancy Specific)

• Starting dose: 500 mg orally twice daily OR 850 mg once daily, given with meals 4
• Titration: Increase in increments of 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 4
• Maximum dose: 2550 mg per day in divided doses (doses above 2000 mg may be better tolerated three times daily with meals) 4

Critical Limitations in Pregnancy

• Metformin is NOT recommended as first-line therapy for gestational diabetes or diabetes in pregnancy—insulin remains preferred 3
• The Endocrine Society recommends avoiding metformin as first-line therapy due to inferior outcomes and safety profiles compared to insulin 3
• When metformin is added to insulin for type 2 diabetes in pregnancy, there is less maternal weight gain and fewer cesarean births, but a doubling of small-for-gestational-age neonates 1
• Approximately 46% of patients on metformin will still require supplemental insulin 9

When Metformin Might Be Considered

• If a patient on insulin refuses to continue injections and requests oral agents, metformin is the preferred alternative (though not ideal) 9
• One RCT showed metformin achieved similar glycemic control with better postprandial glucose after some meals, lower hypoglycemia risk (17.7% vs 55.9% with insulin), and less maternal weight gain 10
• However, this represents a deviation from guideline-recommended care and should only occur after thorough informed consent 3, 9

Common Pitfalls and Caveats

Insulin Management Pitfalls

• Underestimating dose escalation needs: Providers must anticipate that insulin requirements will dramatically increase after 16 weeks—failure to titrate aggressively leads to poor glycemic control 2, 7
• Hypoglycemia risk in first trimester: Enhanced insulin sensitivity and altered counterregulatory responses increase hypoglycemia risk—education for patients and family about prevention, recognition, and treatment is essential 1, 2
• DKA at lower glucose thresholds: Pregnancy is a ketogenic state, and women with type 1 diabetes are at risk for DKA at lower blood glucose levels than when not pregnant 2
• Post-delivery insulin adjustment: Failure to immediately reduce insulin doses after delivery can cause severe hypoglycemia 2, 7

Metformin-Specific Concerns

• Renal function monitoring: Metformin is contraindicated with eGFR <30 mL/min/1.73 m² and not recommended for initiation with eGFR 30-45 mL/min/1.73 m² 4
• Ceiling effect: Unlike insulin (which has unlimited dose escalation), metformin has a maximum effective dose—if insulin was needed initially, oral agents are less likely to succeed 9
• Fetal growth concerns: The doubling of small-for-gestational-age neonates when metformin is added to insulin is a significant safety concern 1

Specialized Care Recommendation

Due to the complexity of insulin management in pregnancy, referral to a specialized center offering team-based care (maternal-fetal medicine specialist, endocrinologist experienced in pregnancy, dietitian, nurse, social worker) is strongly recommended 1, 2