In two randomised trials, researchers evaluated adding metformin to standard care.

Insulin is first-line pharmacotherapy for type 2 diabetes during pregnancy and for gestational diabetes when lifestyle modification has failed to optimise glycaemic control. Two new trials address the potential role of metformin in these scenarios.

US researchers randomised 800 insulin-treated pregnant adults (mean body mass index, 36 kg/m²) with type 2 diabetes to receive either metformin (1000 mg twice daily) or placebo in addition to insulin. The groups did not differ in a composite of various neonatal complications (e.g. perinatal death, preterm birth, neonatal hypoglycaemia), the primary outcome. However, metformin use was associated with significantly lower risk for a large-for-gestational-age infant (26% vs 36%). Adverse events – apart from diarrhoea in metformin recipients – were similar between groups.

In another trial, Irish researchers randomised 500 women with newly diagnosed gestational diabetes to receive lifestyle modification and either metformin (maximum dose, 2500 mg daily) or placebo. The groups did not differ significantly in a composite of insulin initiation or fasting glucose level 5.11 mmol/L or higher at 32 or 38 weeks’ gestation (the primary outcome). However, metformin users were significantly less likely to initiate insulin (38% vs 51%) and less likely to have a large-for-gestational-age infant (7% vs 15%). Metformin use was not associated with preterm delivery. 

Comment: These trials add to a growing body of evidence showing the safety of metformin during pregnancy. In patients who cannot or will not use insulin (the standard of care), metformin appears to be a reasonably safe alternative. However, the trials do not conclusively support routine addition of metformin to lifestyle modification or insulin.

Marie Claire O’Dwyer, MB BCh BAO, MPH, Clinical Assistant Professor in Family Medicine, University of Michigan Medical School, Ann Arbor, USA.

Boggess KA, et al. Metformin plus insulin for preexisting diabetes or gestational diabetes in early pregnancy: the MOMPOD randomized clinical trial. JAMA 2023; 330: 2182-2190.
Dunne F, et al. Early metformin in gesta- tional diabetes: a randomized clinical trial. JAMA 2023; 330: 1547-1556.
Feig DS. Metformin for diabetes in pregnancy: are we closer to defining its role? JAMA 2023; 330: 2167-2169.

This summary is taken from the following Journal Watch titles: General Medicine, Women’s Health, Ambulatory Medicine.