Metformin may prevent betamethasone-induced maternal hyperglycemia, neonatal hypoglycemia

medwireNews: Metformin significantly improves maternal glycemic control and reduces the incidence of neonatal hypoglycemia compared with standard care when given after antenatal betamethasone in women at risk for preterm delivery, study findings indicate.

The results “suggest that metformin could be considered a standard intervention for managing betamethasone-induced hyperglycemia in pregnant women, with the potential to reduce the incidence of neonatal hypoglycemia,” say Enav Yefet (Tzafon Medical Center, Poriya, Israel) and co-investigators.

They explain that “[a]ntenatal corticosteroids (ACSs), particularly betamethasone, are routinely administered to pregnant women at risk of preterm delivery due to their well-established benefits,” but that “ACS administration induces maternal hyperglycemia, which in turn contributes to ACS-induced neonatal hypoglycemia.”

They investigated whether metformin could reduce the rate of neonatal hypoglycemia by mitigating maternal hyperglycemia in 169 pregnant women (mean age 30 years) without diabetes who were given betamethasone from 24.0 to 36.5 gestational weeks due to increased preterm delivery risk.

The women were randomly assigned to receive metformin (425 mg three times daily before meals and 850–1700 mg at 10 pm) or no glucose-lowering treatment for up to 48 hours after the first betamethasone dose.

Yefet and co-authors report in JAMA Network Open that the 84 women given metformin had significantly lower mean total glucose values in the 48 hours after betamethasone injection than the 85 women given no glucose-lowering treatment, at 121 mg/dL versus 127 mg/dL (6.7 vs 7.1 mmol/L). Postprandial glucose levels were also significantly lower with versus without metformin, at a mean of 129 mg/dL versus 138 mg/dL (7.2 vs 7.7 mmol/L).

There were 48 preterm (<37 gestational weeks) infants born to women in the metformin group and 58 born in the untreated group. The researchers found that the risk for neonatal hypoglycemia among preterm infants was a significant 47% lower in the metformin group than in the untreated group, occurring at rates of 21% and 40%, respectively.

“This reduction is notable because it supports the hypothesis that improving maternal glycemic control with metformin can mitigate the risk of neonatal hypoglycemia,” Yefet et al remark.

They add: “This finding is particularly important given the association of neonatal hypoglycemia with adverse neurodevelopmental outcomes, as highlighted in previous studies.”

Overall, metformin was well tolerated, with mild adverse events, which were typically gastrointestinal in nature, reported by 12 (14%) women. There were no cases of maternal hypoglycemia.

The researchers conclude that their findings have “important implications for clinical practice, particularly in settings where preterm delivery is anticipated and ACS administration is routine.”

They suggest that further studies “should focus on the optimal dosing and timing of metformin administration relative to ACSs,” and should compare metformin with other glucose-lowering interventions such as insulin, which “would be valuable to further delineate the most effective and safe approach for both maternal and neonatal outcomes.”

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JAMA Netw Open 2026; 9: e2552807