Gestational diabetes (GDM) is defined as a condition in which hyperglycaemia develops for the first time during pregnancy. Blood glucose-lowering pharmacological treatment is begun if, despite lifestyle changes, the blood glucose level remains above the target. Insulin, which has traditionally been the first-line option, is not transported to the foetus in commonly used doses. However, because insulin treatment is associated with practical inconveniences, tablet medications, particularly metformin, have been increasingly studied. In contrast to insulin, metformin is transported across the placenta into the foetal bloodstream. Although adverse effects on newborns from foetal metformin exposure have not been observed, data on the long-term outcomes of children are limited.

This study aims to investigate the safety of maternal metformin therapy in offspring at the age of 9 years. We studied 172 offspring of mothers who had been randomized to receive either metformin or insulin for GDM. The offspring were born between 2005 and 2010 in Turku or Oulu. We studied the anthropometry, blood pressure, glucose and lipid metabolism, low-grade inflammation, adiponectin, and leptin values of these offspring. To evaluate body composition, visceral adipose tissue volume, and liver fat, we used dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). We studied the offspring’s neuropsychological outcomes with the Wechsler Intelligence Scale for Children (WISC-IV); Developmental Neuropsychological Assessment (NEPSY II); Trail Making Test; Screening Test for Reading, Writing, and Calculus for First to Sixth Grades (Lukilasse 2); and Behavior Rating Inventory of Executive Functioning (BRIEF).

We found that 9-year-old offspring’s anthropometry, body composition, metabolism, and neuropsychological outcomes were similar between the offspring of the mothers who had metformin and those who received insulin treatment for GDM. However, serum HDL cholesterol and adiponectin concentrations were slightly higher and the 2-hour serum glucose concentration in OGTT was slightly lower in boys whose mothers were treated with metformin.

Thus, metformin treatment for GDM seems to be safe for offspring in the long term.