Metformin is associated with lowering maternal hyperglycemia and reducing the risk of neonatal hypoglycemia among pregnant patients at risk of preterm delivery

1. Among pregnant patients at risk of preterm delivery, metformin was associated with lower mean maternal glucose values and a lower rate of neonatal hypoglycemia in preterm infants compared to the control group.

Evidence Rating Level: 1 (Excellent)

Pregnant women at risk of preterm delivery commonly receive antenatal corticosteroid (ACS), particularly betamethasone, to reduce complications of prematurity. However, ACS administration can lead to maternal hyperglycemia, which can contribute to ACS-induced neonatal hypoglycemia. Metformin is commonly used to manage maternal hyperglycemia during pregnancy in women with gestational diabetes. It is unclear whether treating maternal hyperglycemia with metformin reduces the risk of neonatal hypoglycemia in preterm infants. This study thus examined the impact of metformin treatment after betamethasone administration on maternal glycemic control and the incidence of neonatal hypoglycemia in preterm infants. This multicenter, randomized clinical trial conducted from July 1, 2020, to June 30, 2024, in Israel, included pregnant women receiving betamethasone from 24.0 to 36.5 gestational weeks due to increased preterm delivery risk. Participants were randomized 1:1 to metformin (425 mg 3 times daily before meals and 850-1700 mg at 10 pm) or no treatment. The treatment lasted up to 48 hours after the first betamethasone dose (12mg). The primary outcomes were mean maternal glucose values up to 48 hours from the first betamethasone injection and the rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks). Out of the 169 women included (mean [SD] age = 29.7 [5.4] years), 91 were in the metformin group, and 96 women were in the control group. Compared to the control group, the metformin group had lower mean (SD) maternal total and postprandial glucose values (121 [15] vs 127 [17] mg/dL; P = .01; and 129 [22] vs 138 [26] mg/dL; P = .009, respectively). The metformin group also had a lower neonatal hypoglycemia rate (10 [21%] vs 23 [40%]; P = .04) and 47% lower neonatal hypoglycemia risk (relative risk, 0.53; 95% CI, 0.28-0.99) compared to the control group. Mild adverse effects were reported by 12 women. Overall, this study found metformin to be safe and effective in lowering betamethasone-induced maternal hyperglycemia and risk of neonatal hypoglycemia in preterm infants. These findings indicate a potential role for metformin in managing adverse metabolic effects associated with antenatal corticosteroid use among pregnant women. Future research should confirm these findings and determine the best dose and timing in relation to ACS treatment.

Click here to read this study in JAMA Network Open

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