Metformin cuts preterm birth risk among high-risk mothers

A common diabetes medication can reduce the risk of early and preterm births for mothers at high metabolic risk, according to new research led by Monash University.

Published in New England Journal of Medicine Evidence, the study investigated if metformin, a low-cost prescription, oral medication used to manage blood sugar, could help prevent gestational diabetes and other adverse pregnancy outcomes, including early birth. 

Gestational diabetes is characterised by elevated blood sugar during pregnancy and now affects one in five pregnant women in Australia. In severe cases, it can trigger premature labour. 

While metformin's long-term impacts during pregnancy continue to be studied, researchers found metformin didn't prevent gestational diabetes overall, but could offer significant protective benefits against premature delivery.

Preterm birth refers to delivery before 37 weeks, and remains a leading cause of mortality and morbidity for mothers and babies. In Australia, more than 26,000 babies (around 8 per cent of all births) are born prematurely each year, placing infants at risk of respiratory distress, developmental complications, and prolonged stays in neonatal intensive care.

Lead author, Associate Professor Aya Mousa,Head of Diabetes, Metabolic and Reproductive Health Research at the Monash Centre for Health Research & Implementation said women taking metformin had 35 per cent lower odds of giving birth prematurely (before 37 weeks) compared with those receiving a placebo.

"Metformin helps the body use insulin more effectively to lower blood sugar," Associate Professor Mousa said. 

"We found women taking metformin had fewer births before 37 weeks. 

"This included halving the rate of births before 34 weeks - down to 2.2 per cent, compared with 4.4 per cent in the placebo group. 

"Among those who did deliver prematurely, pregnancy was prolonged by an average of 11 days for women on metformin."

Researchers analysed individual patient data from seven randomised, placebo-controlled trials involving 2,297 pregnancies at high metabolic risk, including those with higher body weight, insulin resistance, or polyendocrine metabolic ovarian syndrome (PMOS, previously known as PCOS).

Associate Professor Mousa said metformin's effect on preterm birth warranted further investigation.

"While these findings need to be confirmed in trials specifically designed to investigate preterm birth, including exploring optimal timing for starting metformin, they point to an important potential benefit that warrants further research," Associate Professor Mousa said.

The study forms part of the Metformin in Pregnancy Study (MiPS), a large international collaboration led by Monash researchers, bringing together individual participant data from randomised trials in thousands of women, examining metformin use during pregnancy.

Senior author Professor Helena Teede, Director of the Monash Centre for Health Research & Implementation and an endocrinologist at Monash Health, said the international collaboration helped address an important evidence gap around metformin use in pregnancy, with multiple further questions now being addressed using this vitally important data.

Isolated studies have previously produced mixed findings and have not been large enough to definitively determine metformin effects including in preventing gestational diabetes.

By bringing together the original data from thousands of women across international trials, we could examine individual participants and account for differences such as age, body mass index, blood glucose levels and when treatment began, giving us a clearer picture of metformin's effects during pregnancy."

Professor Helena Teede, Director of the Monash Centre for Health Research & Implementation and endocrinologist at Monash Health

Metformin did not impact other pregnancy outcomes, including birth weight, high blood pressure, pre-eclampsia, induction of labour or Caesarean section.

The broader MiPS collaboration is also investigating the long-term outcomes of metformin exposure during pregnancy.