Aims: We compared the effects of metformin and insulin treatments of gestational diabetes mellitus (GDM) on amino acid metabolism.

Methods: 217 pregnant women diagnosed with GDM were randomized to receive either metformin or insulin. 1H nuclear magnetic spectroscopy was used to determine serum concentrations of alanine, glutamine, glycine, isoleucine, leucine, valine, histidine, phenylalanine, tyrosine, glucose and lactate at the time of diagnosis and at 36 gestational weeks (gw).

Results: Majority of the amino acid concentrations increased from 30 to 36 gw. The rise in alanine (16% vs. 8%, p < 0.0001), isoleucine (11% vs. 5%, p = 0.035) and lactate (29% vs. 14% p = 0.015) was larger in the metformin group compared to insulin group. Baseline alanine, glycine, isoleucine, leucine, valine and tyrosine were positively related to slightly earlier delivery. Alanine at 36 gw was positively associated with birth weight and glutamine with gestational hypertension or preeclampsia. Lactate at 36 gw was not associated with any adverse outcome.

Conclusions: Compared to insulin metformin caused a greater increase in serum alanine, isoleucine and lactate concentrations. Although the observed differences in the metabolic variables were relatively small and not outright concerning, additional studies and follow-up data are required to ensure the safety of metformin use in pregnancy.