Is metformin (metformin hydrochloride) safe during pregnancy?

From the Guidelines

Metformin should be used with caution during pregnancy, as it has been associated with potential risks to the fetus, including increased birth weight and waist circumference, and should only be considered when the benefits outweigh the risks, as stated in the most recent study from 2025 1. The use of metformin during pregnancy is a complex issue, and the decision to use it should be made on a case-by-case basis. While metformin has been shown to be effective in reducing glucose production in the liver and improving insulin sensitivity, it has also been associated with potential risks to the fetus. Some of the key points to consider when deciding whether to use metformin during pregnancy include:

• The potential benefits of metformin in reducing the risk of neonatal hypoglycemia and maternal weight gain, as seen in some studies 1
• The potential risks of metformin, including increased birth weight and waist circumference, as well as the potential for long-term effects on the offspring's glucose metabolism 1
• The importance of carefully monitoring blood glucose levels and adjusting the dose of metformin as needed to minimize the risk of hypoglycemia and other adverse effects 1
• The need for regular prenatal visits and blood glucose monitoring to ensure the best possible outcomes for both the mother and the baby 1 It is also important to note that the American Diabetes Association recommends that metformin be used with caution during pregnancy, and only when the benefits outweigh the risks 1. In terms of the dosage and administration of metformin during pregnancy, the typical dose ranges from 500mg to 2500mg daily, divided into two or three doses with meals. However, the dosage and administration of metformin should be individualized based on the specific needs of the patient, and should be carefully monitored to minimize the risk of adverse effects. Overall, the use of metformin during pregnancy should be approached with caution, and the decision to use it should be made on a case-by-case basis, taking into account the potential benefits and risks, as well as the individual needs of the patient.

From the FDA Drug Label

Limited data with metformin hydrochloride tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy

The use of metformin during pregnancy is not entirely clear due to limited data. However, published studies have not reported a clear association between metformin and major birth defects or miscarriage risk. The primary concern is the risk associated with poorly controlled diabetes mellitus in pregnancy, which increases the risk of diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications. Given the limited data and methodological limitations of the studies, a conservative clinical decision would be to exercise caution when using metformin during pregnancy, considering the potential benefits and risks, and closely monitoring the patient's condition 2.

From the Research

Safety of Metformin During Pregnancy

• Metformin appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight or obese women 3.
• The use of metformin throughout pregnancy in women with polycystic ovary syndrome reduces the rates of early pregnancy loss and preterm labor and protects against fetal growth restriction 3.
• There have been no demonstrable teratogenic effects, intra-uterine deaths or developmental delays with the use of metformin 3.
• Metformin is superior to glyburide and similar to insulin in terms of maternal and fetal outcomes 4.
• Insulin is the preferred pharmacologic treatment according to the American College of Obstetricians and Gynecologists (ACOG), but the Society for Maternal-Fetal Medicine (SMFM) states that outcomes with metformin are similar, and it may also be considered as first-line therapy 4.

Potential Risks and Benefits

• Some studies suggest that metformin may increase the rate of small for gestational age (SGA) births and obesity in childhood 5.
• Metformin reduces hypoglycaemia and macrosomia in infants, but may increase the rate of infants born SGA 5.
• Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy 5.
• The potential advantages of metformin in pregnant women with type 2 diabetes include oral dosing and improved acceptability, lower resource utilization and cost, decreased insulin requirements, less maternal weight gain and less risk of maternal and neonatal hypoglycaemia 6.

Current Research and Recommendations

• There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations 5.
• Further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies 5.
• Prescribing advice for metformin in pregnancy is inconsistent and product information/package inserts (PI) are universally out of date, causing confusion and pushing some women and their clinicians to change from metformin to insulin 6.