What diabetes medications should a female patient with diabetes stop or adjust before conception to minimize fetal risks?

Diabetes Medications to Stop Before Conception

Women with diabetes planning pregnancy must immediately discontinue ACE inhibitors, ARBs, and statins before conception, as these medications are teratogenic and contraindicated in pregnancy. 1

Medications That Must Be Stopped

Absolutely Contraindicated Medications

• ACE inhibitors and ARBs must be discontinued at conception or immediately upon pregnancy recognition due to associations with fetal renal anomalies, oligohydramnios, and fetal death 1, 2, 3
• Statins are pregnancy category X and must be stopped in all sexually active women of childbearing age who are not using reliable contraception 1, 2
• Atenolol should be avoided for hypertension management as it is associated with fetal growth restriction and lower birth weight 2, 3

Most Oral Antidiabetic Agents

• Most oral antidiabetic agents should be discontinued and insulin initiated due to lack of long-term safety data 2
• The exception is that metformin and glyburide have more established safety profiles and may be continued in certain circumstances (see below) 1, 2

Medications That May Be Continued

Insulin (Preferred Agent)

• Insulin is the first-line and preferred medication for managing both type 1 and type 2 diabetes during pregnancy 3, 4
• Insulin does not cross the placenta to a measurable extent, making it the safest option 3
• All women with preexisting diabetes should transition to insulin before conception if not already using it 5

Metformin (May Continue)

• Metformin may be continued during the preconception period and potentially throughout pregnancy 2, 6
• Published studies have not reported a clear association between metformin and major birth defects or miscarriage 6
• Metformin does not increase fetal anomalies and may reduce neonatal hypoglycemia and maternal weight gain 2
• However, there is insufficient information to definitively establish absence of risk due to methodological limitations of available studies 6

Glyburide (May Continue)

• Glyburide is widely used in pregnancy alongside insulin and metformin 2
• Glyburide is more effective than metformin at lowering blood glucose, though it may have higher treatment failure rates 2

Alternative Medications for Comorbid Conditions

Hypertension Management

• Switch to methyldopa, labetalol, or long-acting nifedipine for blood pressure control 2, 3
• Target blood pressure should be 110-135/85 mmHg to reduce risk of accelerated maternal hypertension while minimizing impaired fetal growth 1, 3
• Do not continue ACE inhibitors or ARBs even if blood pressure control is suboptimal 2

Preeclampsia Prevention

• Start low-dose aspirin 100-150 mg/day at 12 to 16 weeks of gestation (81 mg is insufficient) 1, 3
• This reduces the risk of preeclampsia in women with diabetes 1

Timing and Glycemic Targets

Preconception Glycemic Goals

• Achieve A1C <6.5% before conception (ideally <6%) to minimize congenital anomalies, preeclampsia, and other complications 5, 3, 7
• The risk of diabetic embryopathy, especially anencephaly, microcephaly, and congenital heart disease, increases directly with elevations in A1C 1
• Use effective contraception until metabolic optimization is achieved 5, 3

During Pregnancy

• Target A1C <6% during pregnancy if achievable without significant hypoglycemia 1, 3
• Fasting glucose <95 mg/dL, 1-hour postprandial <140 mg/dL, 2-hour postprandial <120 mg/dL 3

Critical Implementation Points

Medication Review Must Be Immediate

• Do not delay medication review - every day of exposure to teratogenic medications increases fetal risk 3
• Review all medications for teratogenic potential before conception in sexually active women not using reliable contraception 2

Multidisciplinary Preconception Care

• Women with preexisting diabetes should be managed in a multidisciplinary clinic including an endocrinologist, maternal-fetal medicine specialist, registered dietitian nutritionist, and diabetes educator when available 1, 5

Additional Preconception Requirements

• Prescribe prenatal vitamins with at least 400 mcg of folic acid (or 4-5 mg for patients with obesity BMI >35) before conception 1, 5
• Screen for diabetic complications including retinopathy, nephropathy, and neuropathy before conception 1
• Comprehensive eye exam is recommended before pregnancy, with monitoring every trimester during pregnancy 1

Common Pitfalls to Avoid

• Do not assume lower doses of ACE inhibitors or ARBs are safe - these medications are absolutely contraindicated regardless of dose 2, 3
• Do not wait until pregnancy is confirmed to stop teratogenic medications in sexually active women not using reliable contraception 2
• Do not continue oral antidiabetic agents (except metformin or glyburide in select cases) without transitioning to insulin, as long-term safety data are lacking 2
• Do not use aspirin 81 mg for preeclampsia prevention - doses >100 mg are required for efficacy 1