NIH grant to study metformin exposure during fetal development

Researchers at Baylor College of Medicine have received a $7.8 million, five-year grant to focus on the impact of prenatal exposure to metformin, a drug prescribed to lower blood sugar in patients with type 2 diabetes. Metformin is prescribed to 50 million Americans annually, including widespread use during pregnancy. The research team will study primates and review the impact of metformin exposure during fetal development.
 
Over the past decade, the use of metformin during pregnancy has steadily expanded beyond the treatment of overt diabetes outside of pregnancy. Its use now includes treatment for prediabetes and obesity, polycystic ovary syndrome, type 2 diabetes and gestational diabetes. With its expanded use, questions of unintended, long-term harm among the offspring exposed to metformin in the womb have arisen. Primates will be administered metformin or a placebo control in addition to a Western-style diet, and the researchers will study the alone and in-combination effects on the offspring
 
“By utilizing a primate model, we have a unique capacity to not only understand how metformin alters both maternal and fetal physiology, but the underlying molecular mechanisms that drive these physiologic changes. Based on our preliminary data, we will be focusing on metformin-driven epigenetic changes to the of the offspring liver, skeletal muscle and other tissues. In addition, we are particularly inspired to further our studies on the role of maternal metformin use in programming persistent alterations in her offspring’s microbiome,” said Dr. Kjersti Aagaard, principal investigator of the study and professor in the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine at Baylor and Texas Children’s Hospital.
 
Aagaard will lead a team of collaborative researchers from multiple institutions that has formed over the last two decades to continue to work on solving the question of metformin’s exposure during fetal and early development. Baylor’s other key investigators on this project include Drs. Melissa Suter, Max Seferovic and Michael Jochum. Collaborating institutions include the Oregon National Primate Research Center, Vanderbilt University, the University of Oklahoma, the University of Oregon and the University of Colorado.
 
“With funding from the NIH and NIDDK, it has been a privilege to work with this truly amazing collaborative team since I was a fellow at the University of Utah. We have developed deep expertise in high-impact pregnancy research in primates and have been fortunate to enable key insights that could not otherwise have occurred. For example, our team’s prior work led to key scientific observations with immediate translational impact by influencing our understanding and recommendations around nutrition during pregnancy. Our team has led in understanding that it is a maternal intake of a Western style diet, more than maternal obesity itself, that programs the fetus to a lifelong risk of insulin resistance, diabetes and obesity,” Aagaard said.
 
This grant is funded by the National Institutes of Health, and the pioneering work will be undertaken at the Oregon National Primate Research Center. Other co-investigators include Dr. Paul Kievit, Dr. Maureen Gannon, Dr. Jed Friedman, Dr. Carrie McCurdy and Dr. Stephanie Wesalowski.