Early introduction of metformin yields maternal and neonatal health benefits in women with gestational diabetes
Ireland: The early introduction of metformin in women with gestational diabetes mellitus (GDM) is associated with significant maternal and neonatal benefits with no increase in adverse perinatal events, a Phase III trial has shown.
The study, however, revealed that the early introduction of metformin failed to reduce the composite of insulin initiation or elevated fasting glucose at week 32 or 38 in this population. The findings were presented at the annual meeting of the ADA (American Diabetes Association), held from June 23 to 26 in San Diego and subsequently published in the Diabetes Journal.
Considering that the optimal approach for GDM management is uncertain, Fidelma P. Dunne from Galway, Ireland, and colleagues sought to determine whether the early introduction of metformin (at diagnosis) plus lifestyle modification was superior to standard care (lifestyle modification alone) in the EMERGE trial.
EMERGE is a phase III, superiority, parallel-group trial. Five hundred thirty-five women with gestational diabetes were randomly assigned to metformin (initiated before 28 weeks +6 days gestational age) plus lifestyle modification (n=268) or placebo plus lifestyle modification (n=267) between 2017 and 2022. The researchers compared the effectiveness of 500 mg per day of metformin, titrated to 2,500 mg, to placebo. The primary outcome was the composite of insulin initiation or fasting glucose ≥5.1 mmol/L at week 32 or 38.
The authors reported the following findings:
- There was no significant difference in the primary outcome between metformin and placebo treatments (56.8% vs 63.7%; RR=0.89).
- Insulin initiation was significantly lower in the metformin (38.4%) versus the placebo (51.1%) group (RR 0.75).
- Compared to placebo, metformin-treated women achieved better glycemic control (HbA1C at 38 weeks; 33.9 vs 35 mmol/mol) and gained less weight between randomization and delivery (0.8kg vs 2.0kg), while infants were less likely to weigh >4000g (7.6% vs 14.8%).
- There was no significant difference in infants weighing <2500g (6.1% vs 3.4%), in infants needing NICU admission (15.3% vs 12.5%) or in infants born preterm <37weeks (9.2% vs 6.5%) in the metformin versus placebo groups.
"The trial showed important benefits to maternal weight gain, maternal glycemic control, and infant size in terms of large for gestational age and macrosomia without any increase in low birth weight or small for gestational age," the researchers wrote.
"There was no increase in preterm birth, spontaneous or iatrogenic, and no excess of any other neonatal and maternal morbidities which may have implications for GDM treatment in countries where insulin is difficult to get or is not affordable."
Reference:
FIDELMA P. DUNNE, ALBERTO ALVAREZ-IGLESIAS, CHRISTINE NEWMAN, ANDREW SMYTH, MARIE BROWNE, DECLAN DEVANE, PADDY GILLESPIE, MARTIN O'DONNELL; 183-LB: A Randomized Placebo-Controlled Trial of the Effectiveness of Early Metformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE). Diabetes June 20 2023; 72 (Supplement_1): 183–LB. https://doi.org/10.2337/db23-183-LB
