Maternal use of Metformin for gestational diabetes not tied to adverse neonatal outcomes

The study, published in Acta Diabetologica, states that metformin may benefit women with gestational diabetes at high neonatal hypoglycemia risk, women unable to afford or use insulin safely, and women who want to limit fetal and maternal weight gain.

Neonates exposed to in-utero metformin had lower weight at birth than those whose mothers had insulin exposure. Macrosomia risk is substantially lower by 30% when GDM is treated with metformin versus insulin. There is no resultant increase in the risk of being born large for gestational age (LGA) or small for gestational age (SGA). Neonates of metformin-treated women, despite being born at lower average birth weight, were not shown to have an increased incidence of neonatal adverse outcomes. Metformin, in contrast, significantly reduced the incidence of neonatal intensive care unit admission and the risk of neonatal hypoglycemia.

Women with uncontrolled gestational diabetes mellitus (GDM) have high-risk pregnancies, and some of GDM's adverse effects may also impact the fetus, including macrosomia (birth weight of > 4000 g), fetal anomalies, metabolic disorders, fetal distress, hyperbilirubinemia, growth imbalance, and some long-term complications. Because insulin cannot cross the placenta, it has traditionally been the gold standard for GDM treatment and allows precise glucose control. However, insulin therapy has some disadvantages, including risks of hyperbilirubinemia and hypoglycemia, the need for multiple injections, rising insulin costs, and lack of affordability.

In clinical practice, metformin is a commonly used antihyperglycemic drug with excellent efficacy concerning weight loss and glycemic control, reasonable price, and good tolerance. Currently, several organizations support metformin use as an alternative to insulin. However, recent long-term studies of offspring have yielded conflicting results.

Therefore, Xuemei Lin from Sichuan University in Sichuan, China, and colleagues performed an updated meta-analysis to compare the safety and efficacy of metformin versus insulin for short-term neonatal outcomes in GDM treatment. Their objective was to determine whether metformin is superior to insulin in terms of inducing neonatal adverse effects and altering neonatal growth during GDM treatment. Addressing this issue becomes vital as the number of pregnancies exposed to metformin increases worldwide.

For this purpose, the researchers performed a comprehensive search of electronic databases. Two reviewers extracted the data by using a random-effects model. A total of 24 studies comprising 4355 people met the inclusion criteria and were included in the quantitative analyses.

The authors reported the following findings:

• Metformin, unlike insulin, lowered neonatal birth weights (mean difference − 122.76 g), the risk of macrosomia (risk ratio [RR] 0.68), the incidence of neonatal intensive care unit admission (RR 0.73), and the incidence of neonatal hypoglycemia (RR 0.65).
• Subgroup analysis based on the maximum daily oral metformin dose indicated that metformin-induced neonatal birth weight loss was independent of the oral dose.

"Results from the meta-analysis add to the evidence that metformin may specifically be useful in women with GDM who are at high risk for neonatal hypoglycemia, women unable to afford insulin, and those who want to limit fetal and maternal weight gain," the authors wrote in their study.

Metformin can effectively lower incidences of neonatal hypoglycemia, macrosomia, lower neonatal birth weight and admission to the neonatal ICU (NICU) compared with insulin without an increased neonatal adverse outcomes risk.

"Whether metformin's effect on neonatal birth weight is linked with the oral metformin dose requires further investigation in large-scale trials," the team concluded.

Reference:

Sheng, B., Ni, J., Lv, B. et al. Short-term neonatal outcomes in women with gestational diabetes treated using metformin versus insulin: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol (2023). https://doi.org/10.1007/s00592-022-02016-5