Maternal Metformin Treatment Improves Developmental and Metabolic Traits of IUGR Fetuses

Abstract

Metformin is an anti-hyperglycemic drug widely used for the treatment of insulin resistance and glucose intolerance and is currently considered for preventing large-for-gestational-age (LGA) offspring in pregnant women affected by obesity or diabetes. Our hypothesis was the opposite—metformin may be used for improving the development of offspring affected by intrauterine growth restriction (IUGR) and preventing the appearance of small-for-gestational-age (SGA) neonates in non-obese and non-diabetic but malnourished pregnancies. The current study, performed in a swine preclinical model of IUGR by undernutrition, showed that fetuses in the treated group showed no significant increases in body-weight, but showed a significantly higher weight of the brain, the total thoracic and abdominal viscera, the liver, the kidneys, the spleen, and the adrenal glands. Maternal metformin treatment was also related to significant increases in the fetal plasma concentration of parameters indicative of glycemic (glucose and fructosamine) and lipid profiles (triglycerides). Overall, these results suggest a protective effect of the treatment on the developmental competence of the fetuses. These findings may be of high value for human medicine in case of maternal malnutrition, since metformin is a cheap drug easily available, but also in case of placental deficiency, since metformin seems to improve placental development and function.