Early Metformin treatment in gestational diabetes shows mixed results in clinical trial

A recent double-blind, placebo-controlled clinical trial conducted in Ireland has shown that early initiation of metformin during gestation did not significantly reduce the need for insulin treatment or improve fasting blood sugar levels in pregnant individuals with gestational diabetes.

The trial published in JAMA involved 510 participants (comprising 535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. These individuals were randomly assigned to receive either metformin (up to 2500 mg daily) or a placebo in addition to their usual prenatal care.

Results from the trial, which concluded in September 2022, showed that the primary composite outcome did not significantly differ between the metformin group and the placebo group. In the metformin group, this outcome occurred in 56.8% of pregnancies, while in the placebo group, it occurred in 63.7% (a between-group difference of -6.9%).

Although the primary outcome did not show a statistically significant difference, there were notable findings in secondary outcomes. In particular, several secondary maternal outcomes favored the metformin group, including a delay in the need for insulin initiation, self-reported capillary glycemic control, and healthier gestational weight gain.

However, secondary neonatal outcomes displayed differences between the two groups. Neonates in the metformin group tended to have lower birth weights, with a lower proportion weighing over 4 kg and having smaller crown-heel lengths. Importantly, there were no significant differences in critical neonatal parameters such as the need for intensive care, respiratory distress requiring support, neonatal jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or Apgar scores at 5 minutes.

Reference: Dunne F, Newman C, Alvarez-Iglesias A, et al. Early Metformin in Gestational Diabetes: A Randomized Clinical Trial. JAMA. Published online October 03, 2023. DOI: 10.1001/jama.2023.19869