A RECENT study conducted across 25 centres in the Netherlands has raised concerns about the effectiveness of oral glucose-lowering medications for gestational diabetes compared to insulin. The research, carried out between June 2016 and May 2023, focused on whether a sequential treatment strategy using metformin and glyburide was as effective as insulin in preventing large-for-gestational-age (LGA) infants.
The trial involved 820 participants with singleton pregnancies between 16 and 34 weeks’ gestation, all of whom had failed to achieve adequate glycaemic control through dietary changes alone. Participants were randomly assigned to receive either oral medications or insulin. Among the oral treatment group, metformin was the initial therapy, followed by glyburide if required, with insulin used only if neither medication achieved the desired glucose targets.
Results showed that 23.9% of infants born to participants in the oral treatment group were classified as LGA, compared with 19.9% in the insulin group. This 4% difference exceeded the pre-defined noninferiority margin of 8%, meaning the oral treatment strategy did not meet the criteria for equivalence to insulin.
The study also noted that maternal hypoglycaemia occurred in 20.9% of those treated with oral medications compared with 10.9% in the insulin group, highlighting a potential safety concern. However, no significant differences were observed in other secondary outcomes, including rates of pre-eclampsia, caesarean delivery, or neonatal intensive care unit admissions.
The findings underscore the limitations of oral glucose-lowering medications for managing gestational diabetes, particularly regarding infant birth weight. While oral medications like metformin and glyburide remain more convenient and less invasive than insulin, their inability to achieve comparable outcomes raises questions about their use as first-line therapies.
Experts suggest that while oral treatments may still play a role in some cases, insulin remains the gold standard for reducing risks associated with gestational diabetes. Future research may explore ways to optimise oral medication regimens to improve outcomes for both mothers and infants.
Reference
Rademaker D et al. Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes. JAMA. 2025;DOI:10.1001/jama.2024.23410.
