Metformin During Pregnancy: What the Evidence Shows

What does the evidence say about metformin during pregnancy?

1. Metformin is used for type 2 diabetes, PCOS-related insulin resistance, and gestational diabetes. Taking it during pregnancy is not expected to raise the chance of birth defects or miscarriage above the background rate, which is about 3 in 100 pregnancies regardless. 1
2. In a randomized trial of 751 pregnant women with gestational diabetes, neonatal outcomes were similar between the metformin and insulin groups. Metformin was linked to less maternal hypoglycemia and less weight gain, though about 46 percent of the metformin group eventually needed insulin added for full glucose control, and 93 percent stayed on metformin through the end of pregnancy. 2
3. For PCOS specifically, continuing metformin through the first trimester rather than stopping at a positive pregnancy test has been linked to a markedly lower miscarriage rate: 10.8 percent versus 42.2 percent in one randomized trial, and 11.6 percent versus 36.3 percent in a meta-analysis of observational studies, at typical doses of 1,000 to 2,000 mg a day. 3
4. Metformin passes into breast milk in only small amounts, with breastfed infants receiving roughly 0.25 to 0.65 percent of the mother's weight-adjusted dose. A study following 92 mothers and 111 infants found no difference in growth, development, or illness rates at 3 and 6 months between breastfed and formula-fed infants of mothers taking metformin. 4
5. Metformin should be used with caution while nursing a newborn or premature infant, or a baby with reduced kidney function, and the evidence does not support using metformin to increase milk supply despite occasional use for that purpose. 4

Is metformin safe in each trimester?

• First trimester. For PCOS, metformin is often already in use before conception, and trial data favor continuing it through the first trimester rather than stopping at a positive pregnancy test: one randomized trial found a miscarriage rate of 10.8 percent among women who continued it versus 42.2 percent among those who stopped early.
• Second trimester. If gestational diabetes is identified with a glucose tolerance test, metformin is one of two medication options alongside insulin when diet and exercise alone aren't enough. In one large trial, 93 percent of women who started metformin stayed on it for the rest of the pregnancy, with less maternal hypoglycemia than the insulin group.
• Third trimester. About 46 percent of women who start metformin for gestational diabetes eventually need insulin added for full glucose control as insulin resistance tends to rise later in pregnancy. Birth weight and the chance of a larger-than-average baby were similar between the metformin and insulin groups in trial data.