Metformin use during pregnancy not associated with adverse outcomes in children

Use of metformin for diabetes in pregnancy does not appear to be associated with adverse outcomes in children, a recent industry-conducted study found.

Researchers in Finland performed a register-based cohort study to examine whether maternal exposure to metformin during pregnancy is linked to long- or short-term adverse outcomes in children. They looked at singleton children born from 2004 through 2016 whose mothers took metformin, insulin, or both during pregnancy. Insulin alone was considered the control. Children whose mothers had type 1 diabetes were excluded.

The study's primary outcomes were long-term obesity, hypoglycemia, hyperglycemia, diabetes, hypertension, polycystic ovary syndrome (in girls only), and challenges in motor-social development in children; secondary outcomes were adverse outcomes at birth, including large for gestational age, small for gestational age, preterm birth, neonatal mortality, neonatal hypoglycemia, hyperglycemia, and major congenital abnormalities. Merck KGaA funded and commissioned the study from IQVIA, and all but one author were employees of either company. Results were published Jan. 5 by BMJ Open Diabetes Research & Care.

Overall, the study included data on 10,129 children, 3,967 exposed to metformin in utero, 5,273 exposed to insulin, and 889 exposed to both. In the main analysis and in sensitivity analyses, no difference in the studied long-term outcomes was seen between exposure to metformin or combination treatment versus insulin. Exposure to metformin was associated with increased risk of small for gestational age, while combination treatment was associated with increased risk of large for gestational age, preterm birth, and hypoglycemia. There was no increased risk seen for neonatal mortality, hyperglycemia, or major congenital anomalies.

The researchers noted that they could not determine whether metformin and insulin were used sequentially or concurrently in the combination treatment group and that the mean follow-up of 3.5 years for the cohort overall was relatively short, among other limitations. “Although a longer median follow-up time could bring better confidence to its findings, this study found no increased long-term risk of obesity, hypoglycemia, hyperglycemia, diabetes, or challenges in [motor-social development] associated with in utero exposure to metformin (alone or in combination with insulin), compared with insulin alone,” the authors wrote. “The observed increased risk of [small for gestational age] associated with metformin alone versus insulin may warrant caution for use in pregnancies with risk of fetal undernutrition.”