# Metformin, Maternal Glycemic Control, and Neonatal Hypoglycemia After Antenatal Steroids: A Randomized Clinical Trial

## TL;DR

Metformin helps control maternal blood sugar and reduces neonatal hypoglycemia in preterm infants after steroid treatment.

## Contribution

Metformin is shown to safely reduce betamethasone-induced maternal hyperglycemia and neonatal hypoglycemia in preterm births.

## Key findings

- Metformin significantly lowered maternal glucose levels compared to standard care.
- Neonatal hypoglycemia occurred in 21% of metformin group infants versus 40% in the control group.
- Mild gastrointestinal side effects were reported in 14% of metformin-treated women.

## Abstract

Does metformin treatment after betamethasone administration improve maternal glycemic control and reduce the incidence of neonatal hypoglycemia in preterm infants?

In this randomized clinical trial of 169 pregnant women receiving betamethasone, metformin significantly improved maternal glycemic control and reduced the incidence of neonatal hypoglycemia compared with standard care, indicating a potential therapeutic benefit in this population.

Metformin may be a safe and effective strategy to prevent betamethasone-induced maternal hyperglycemia and neonatal hypoglycemia in preterm births.

This randomized clinical trial of pregnant women examines whether metformin can reduce the rate of neonatal hypoglycemia in preterm infants whose mothers receive betamethasone by mitigating maternal hyperglycemia.

Although betamethasone reduces complications of prematurity, it can cause maternal hyperglycemia and neonatal hypoglycemia. Metformin effectively treats maternal hyperglycemia and has been shown to decrease neonatal hypoglycemia in women with gestational diabetes.

To evaluate the impact of metformin treatment after betamethasone administration on maternal glycemic control and the incidence of neonatal hypoglycemia in preterm infants.

This multicenter, open-label randomized clinical trial was conducted from July 1, 2020, to June 30, 2024, at 3 medical centers in Israel. Pregnant women receiving betamethasone from 24.0 to 36.5 gestational weeks due to increased preterm delivery risk were studied. Women with diabetes were excluded.

Participants were randomized 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. Capillary glucose was measured before meals (preprandial), 90 minutes after starting meals (postprandial), and at 10 pm.

The primary end points were the mean maternal glucose values up to 48 hours from first betamethasone injection and the rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks).

A total of 169 women (mean [SD] age, 29.7 [5.4] years), including 84 with 48 preterm infants in the metformin group and 85 with 58 preterm neonates in the control group, were included in the study. Mean (SD) maternal total and postprandial glucose values were significantly lower in the metformin group (121 [15] vs 127 [17] mg/dL; P = .01; and 129 [22] vs 138 [26] mg/dL; P = .009, respectively). Neonatal hypoglycemia rate was lower in the metformin group (10 [21%] vs 23 [40%]; P = .04; relative risk, 0.53; 95% CI, 0.28-0.99). Mild adverse effects, mostly gastrointestinal, were reported by 12 women (14%).

In this randomized clinical trial, metformin was safe and effective in preventing betamethasone-induced maternal hyperglycemia and neonatal hypoglycemia. Metformin should be considered as a treatment option for women who receive antenatal corticosteroids to prevent their related adverse effects.

ClinicalTrials.gov Identifier: NCT04332393