Study examines metformin use in pregnant women with gestational diabetes

By Rebecca Jenkins

Early metformin initiation does not improve glycaemic control or reduce insulin use in pregnant women with gestational diabetes, an Irish study finds.

Pharmacotherapy for glucose control in gestational diabetes was currently only prescribed following unsuccessful lifestyle management, researchers wrote in JAMA, but this resulted in some people experiencing weeks of hyperglycaemia during their pregnancy.

‘Routine earlier initiation of metformin (at the time of diagnosis) may improve glycaemic control, reduce the need for insulin therapy, and may have clinical advantages beyond glycaemic control, such as reducing gestational weight gain,’ the researchers wrote.

To test the theory, the researchers enrolled 510 pregnant participants aged 18 to 50 years, who were newly diagnosed with gestational diabetes, and randomised them to placebo or metformin (up to 2500 mg/day) in addition to usual care.

The participants had a singleton pregnancy and were diagnosed up to 28 weeks (+6 days) gestation according to the WHO 2013 gestational diabetes criteria.

The researchers found the composite outcome of insulin initiation and a fasting glucose level of 5.1mmol/L or greater at gestational weeks 32 or 38 was not significantly different between the groups.

‘Secondary outcomes of maternal glycaemic control, weight gain, and infant size were lower in the metformin group,’ they noted.

‘Prespecified secondary outcome data support further investigation of metformin in larger clinical trials,’ they wrote.

Dr Arianne Sweeting, Maternal Metabolic Health Lead in Endocrinology at Royal Prince Alfred Hospital and The University of Sydney, said this was a well-conducted trial with a pragmatic primary outcome.

‘Their null finding shows that early metformin alone was not sufficient in their predominantly white, higher body mass index cohort,’ she told Medicine Today.

Dr Sweeting said the results were consistent with an earlier study of women with gestational diabetes showing that almost 50% of participants given metformin also needed insulin to achieve glucose targets, underscoring the high degree of insulin resistance as pregnancy progresses.

‘The secondary outcomes of the latest study are merely hypothesis generating, but the benefits shown with time to insulin initiation, self-reported capillary glycaemic control, and gestational weight gain would be consistent with previous research, including in women with type 2 diabetes, as would the trend to lower birth size, less macrosomia/large for gestational age,’ she added.

Insulin remained the first-line pharmacotherapy for gestational diabetes in Australia, Dr Sweeting said, but metformin was increasingly being used, particularly in rural and remote areas.

‘Due to the potential concerns regarding long-term metabolic programming effects of placental transfer of metformin to the fetus, with previous evidence showing a link with accelerated growth in the offspring, what is really needed is longer-term, adequately powered studies assessing offspring anthropometry and metabolic parameters in diverse populations,’ Dr Sweeting said.

Given this trial and the previous study showing metformin was often inadequate as a single agent in gestational diabetes, Dr Sweeting suggested research evaluating metformin together with insulin would be the most informative for clinical practice. 

JAMA 2023; doi: 10.1001/ jama.2023.19869.