Diabetes Medicines During Pregnancy

Diabetes medicines in pregnancy aim for near-normal glucose with minimal hypoglycaemia. Poor control causes miscarriage, congenital malformation (neural tube, cardiac), macrosomia, stillbirth and neonatal hypoglycaemia. Insulin is the cornerstone in type 1 and type 2 diabetes; oral agents have a limited role.

Glucose targets. Fasting 3.9 to 5.3 mmol/L; 1 hour after meals under 7.8 mmol/L or 2 hours under 6.4 mmol/L; avoid any value under 3.9 mmol/L. Continuous glucose monitoring target time in range (3.5 to 7.8 mmol/L) over 70%.

Preconception. HbA1c under 48 mmol/mol (6.5%) before conception where safely achievable; folic acid 5 mg daily; stop ACE inhibitors, angiotensin receptor blockers and statins; retinal and renal assessment.

Insulin, type 1 and type 2. Basal-bolus regimen: long-acting insulin (isophane insulin twice daily, or detemir or glargine once or twice daily) with rapid-acting insulin (lispro, aspart or soluble human insulin) before meals.

• Approximate total daily requirement in type 2 diabetes: 0.7 units/kg to 18 weeks, 0.8 units/kg from 18 to 26 weeks, 0.9 units/kg from 26 to 36 weeks, 1.0 units/kg from 36 weeks.
• Type 1 diabetes: needs fall by 10 to 20% in the first trimester (hypoglycaemia risk; nausea), then rise steeply, often 1.5 to 2 times the pre-pregnancy dose by 36 weeks.
• Titrate every 2 to 3 days by 10% for persistent out-of-range values.

Metformin. 500 mg orally once daily with food, increasing weekly to 2 g daily in 2 to 3 doses (maximum 2.5 to 3 g daily). Continue in type 2 diabetes and polycystic ovary syndrome until at least the first trimester if glucose control is good; add insulin when targets are missed.

Glibenclamide (glyburide). 2.5 mg orally once daily, increased to 10 mg twice daily (maximum 20 mg daily), second line for gestational diabetes where insulin is refused or unavailable; risk of neonatal hypoglycaemia and macrosomia exceeds that of metformin.

Gestational diabetes. Diet and exercise for 1 to 2 weeks. Start metformin if targets are missed; add insulin if targets are still missed, or start insulin at once if fasting glucose is 7.0 mmol/L or more at diagnosis (or 6.0 mmol/L or more with macrosomia). Start with isophane insulin 0.1 to 0.2 units/kg at night and rapid-acting insulin 4 to 6 units with meals.

Aspirin. 150 mg at night from 12 weeks to 36 weeks for pre-eclampsia prevention.

Labour and birth. Capillary glucose hourly; target 4 to 7 mmol/L. Start a variable-rate IV insulin infusion with 5% glucose in sodium chloride 0.9% if glucose exceeds 7 mmol/L in labour in type 1 diabetes, and in gestational diabetes when targets are missed. Start corticosteroid cover with an insulin infusion (rate raised for 48 to 72 hours).

Hypoglycaemia. Conscious: 15 to 20 g fast-acting glucose orally, recheck at 15 minutes. Unconscious: glucose 10% IV 150 to 200 mL over 15 minutes, or glucagon 1 mg IM.

Diabetic ketoacidosis. Can occur at glucose under 11 mmol/L in pregnancy. Fixed-rate insulin 0.1 units/kg/hour, IV fluids, potassium replacement and foetal assessment.

After birth.

• Gestational diabetes: stop all treatment; fasting glucose or HbA1c at 6 to 13 weeks, then yearly.
• Type 1 diabetes: return to pre-pregnancy insulin dose or reduce by about 50% on day 1 (insulin needs fall sharply after placental delivery; breastfeeding lowers needs further).
• Type 2 diabetes: metformin and insulin continue; review other agents.

Avoid. Sulphonylureas other than glibenclamide, SGLT2 inhibitors, GLP-1 receptor agonists and tirzepatide (stop at least 2 months before conception), DPP-4 inhibitors, pioglitazone, ACE inhibitors, angiotensin receptor blockers, statins.

Adverse effects. Hypoglycaemia (hypoglycaemia unawareness worsens in the first trimester), weight gain, lipohypertrophy; metformin gastrointestinal upset and rare lactic acidosis.

Interactions. Corticosteroids (antenatal betamethasone) and tocolytics (terbutaline) raise glucose for 3 to 5 days. Labetalol and beta-blockers mask hypoglycaemia. Antipsychotics (olanzapine, quetiapine) raise glucose.

Special groups.

• Kidney impairment: reduce insulin doses; avoid metformin when eGFR is under 30 mL/min and halve the dose at 30 to 45 mL/min.
• Liver impairment: reduce insulin; avoid metformin in decompensated disease.
• Breastfeeding: insulin, metformin and glibenclamide are compatible.
• Regional: human insulin (isophane and soluble) is the most available in many East African facilities and is acceptable; analogue use depends on cost and supply. Offer glucose testing strips and education early, as access is limited.

Monitoring. Capillary glucose fasting and 1 hour after each meal (and before meals and at bedtime on basal-bolus insulin). HbA1c every 4 to 8 weeks in pre-existing diabetes (target under 48 mmol/mol, 6.5%, where achievable without hypoglycaemia). Retinal screening at booking, 16 to 20 weeks and 28 weeks; renal function and urine protein at booking. Foetal growth scans every 2 to 4 weeks from 28 weeks. Ketone testing when unwell.

Stopping rules. Reduce insulin immediately after birth (type 1 diabetes: back to the pre-pregnancy dose or about 50% less); stop metformin if eGFR falls under 30 mL/min or with sepsis, dehydration or contrast exposure.

Referral and escalation. Refer to a joint diabetes and antenatal clinic within 1 week of diagnosis and for any pre-existing diabetes before conception. Admit for severe hypoglycaemia, ketoacidosis, persistent vomiting on insulin or rapid foetal growth acceleration.