Metformin prevents ACS-induced maternal hyperglycaemia, neonatal hypoglycaemia

The use of metformin following antenatal corticosteroid (ACS), specifically betamethasone, significantly improves maternal glucose levels and lowers the risk of neonatal hypoglycaemia in preterm infants, according to a recent study.

“The findings from this study suggest that metformin could be considered a standard intervention for managing betamethasone-induced hyperglycaemia in pregnant women, with the potential to reduce the incidence of neonatal hypoglycaemia,” said the researchers.

“This finding has important implications for clinical practice, particularly in settings where preterm delivery is anticipated and ACS administration is routine,” they noted.

The study included 169 pregnant women (mean age 29.7 years) at risk of preterm delivery, who received 12 mg of intramuscular betamethasone administered between 24 and 36.5 gestational weeks. Participants were randomly assigned to the metformin* group (n=84) or control group (n=85), with 48 and 58 preterm neonates assigned to each group, respectively. [JAMA Netw Open 2026;doi:10.1001/jamanetworkopen.2025.52807]

Compared with the control group, the metformin group had significantly lower mean maternal total glucose (121 vs 127 mg/dL; p=0.01) and mean postprandial glucose (129 vs 138 mg/dL; p=0.009) levels, “which aligns with existing literature on the efficacy of metformin in treating gestational diabetes,” the researchers noted.

In turn, preterm neonates born to mothers treated with metformin had a significantly reduced risk of hypoglycaemia compared with those born to mothers who did not receive treatment (21 percent vs 40 percent; p=0.04), indicating a relative risk of 0.53. “This reduction is notable because it supports the hypothesis that improving maternal glycaemic control with metformin can mitigate the risk of neonatal hyperglycaemia.”

Taken together, these findings are “clinically important because maternal hyperglycaemia has been directly linked to an increased risk of neonatal hypoglycaemia, which can lead to severe neonatal complications,” said the researchers. “By addressing maternal hyperglycaemia, this study provides evidence of a preventive approach that could be integrated into clinical practice.”

Other maternal and neonatal outcomes were comparable between the two groups, noted the researchers.

In terms of safety, only 14 percent of women in the metformin group experienced mild gastrointestinal side effects, of which 10 percent discontinued treatment.

Metformin was well tolerated, with no events of maternal hypoglycaemia (defined as glucose ≤60 mg/dL) reported in either group, the researchers noted.

Overall, “this study found that metformin is safe and effective in preventing ACS-induced maternal hyperglycaemia and neonatal hypoglycaemia,” said the researchers.