What is the issue?

We examined whether metformin has a role in improving health outcomes for pregnant women with obesity or who are overweight, and their babies. We considered possible benefits, adverse effects and healthcare system costs.

Body mass index (BMI), calculated from a person’s height and weight, is used to classify someone as having normal weight (BMI less than 25 kg/m²), being overweight (BMI 24.9 kg/m² to 30 kg/m²) or having obesity (BMI above 30 kg/m²). Women with obesity or who are overweight are more likely than women of normal weight to experience complications like high blood pressure and gestational diabetes during pregnancy. They are also at increased risk of needing a caesarean or developing infection after birth. Their babies are more likely to experience health problems, requiring admission to the neonatal unit or intensive care, have low blood sugar, or problems breathing immediately after birth.

Women with obesity or who are overweight may have some features of diabetes that may contribute to problems during pregnancy and birth. They may not process dietary carbohydrates and sugars efficiently, and are more likely to be resistant to the hormone insulin, released by the pancreas after eating, helping muscles use blood glucose (sugar) for energy. Glucose circulates in the blood for longer, providing excess energy to the growing baby. There is an increased risk of developing diabetes in pregnancy and women may have low levels of inflammatory hormones and proteins circulating in the body. Improving diet and increasing exercise have had a very small effect on reducing weight gain during pregnancy and no effect on complications.

Metformin, a drug used to treat diabetes, reduces the amount of glucose the liver releases into the blood and makes the body more sensitive to insulin. Metformin may help a woman’s body use insulin more effectively and reduce the chance that her baby will grow large-for-gestational age.

What evidence did we find?

We searched for evidence (October 2017) and found three randomised controlled studies (1099 pregnant women) comparing metformin tablets with placebo (dummy) tablets taken by mouth from 10 to 20 weeks of pregnancy until birth. The studies involved women with obesity; we therefore could not assess the effect of metformin in women who are overweight.

Women who were given metformin or placebo during pregnancy had a similar risk of a baby being born large-for-gestational age (measured in weeks since last period). Metformin probably makes little or no difference in the risk of women developing gestational diabetes. Metformin may also have little or no difference in the risk of women developing gestational hypertension (high blood pressure) or pre-eclampsia.

Women who were given metformin may gain slightly less weight during pregnancy, but are more likely to experience diarrhoea. There were no other important differences identified for other maternal outcomes including, caesarean birth, giving birth before 37 weeks of pregnancy, shoulder dystocia (a birth complication where the baby’s shoulder gets stuck), perineal trauma (damage to the area between the woman’s vagina and the anus), or heavy bleeding after the baby has been born.

Babies of women who were given metformin had similar birthweight to babies of women who were given placebo. We did not identify any other important differences for other infant outcomes of interest: hypoglycaemia (low blood sugar); hyperbilirubinaemia (jaundice); Apgar score at five minutes (a measure of newborn well-being); or death of the baby before or after being born. One study reported similar rates of admission to neonatal intensive care between groups.

What does this mean?

There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving outcomes for the mother and her baby. Metform was associated with increased risk of adverse effects, particularly diarrhoea.

A small number of studies are included in this review and no study included women categorised as ‘overweight’, or looked at metformin in combination with another treatment.

More research is needed to evaluate the role of metformin in pregnant women with obesity or who are overweight, as a strategy for improving maternal and infant health, either alone or as an additional intervention.