Skip to main content
ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #351976
Title: A cautionary response to SMFM statement: Pharmacological treatment of gestational diabetes

Author
item BARBOUR, LINDA - University Of Colorado
item SCIFRES, CHRISTINA - University Of Oklahoma
item VALENT, AMY - Oregon Health & Science University
item FREIDMAN, JACOB - University Of Colorado
item BUCHANAN, THOMAS - University Of Southern California
item COUSTAN, DAN - University Arkansas For Medical Sciences (UAMS)
item AAAGARD, KJERSTI - Baylor College Of Medicine
item THORNBURG, KENT - University Of Oregon
item CATALANO, PATRICK - Tufts University
item GALAN, HENRY - University Of Colorado
item HAY, WILLIAM - University Of Colorado
item FRIAS, ANTONIO - Oregon Health & Science University
item SHANKAR, KARTIK - University Of Colorado
item SIMMONS, REBECCA - University Of Pennsylvania
item MOSES, ROBERT - Wollongong Hospital
item SACKS, DAVID - Kaiser Permanente
item LOEKEN, MARY - Harvard Medical School

Submitted to: American Journal of Obstetrics and Gynecology
Publication Type: Other
Publication Acceptance Date: 6/20/2018
Publication Date: 6/27/2018
Citation: Barbour, L., Scifres, C., Valent, A., Freidman, J., Buchanan, T., Coustan, D., Aaagard, K., Thornburg, K., Catalano, P., Galan, H., Hay, W., Frias, A., Shankar, K., Simmons, R., Moses, R., Sacks, D.A., Loeken, M. 2018. A cautionary response to SMFM statement: Pharmacological treatment of gestational diabetes. American Journal of Obstetrics and Gynecology. 9378(18): 30529-30535. http://doi.org/10.1016/j.ajog.2018.06.013.
DOI: https://doi.org/10.1016/j.ajog.2018.06.013

Interpretive Summary:

Technical Abstract: Use of oral agents to treat gestational diabetes (GDM) remains controversial. Recent SMFM recommendations assert that metformin may be a safe first line alternative to insulin for GDM treatment. However, several issues should give pause to metformin’s widespread adoption. Fetal concentrations of metformin are equal to maternal high, and metformin has growth inhibitory and anti-cancer effects, suppresses mitochondrial respiration, and inhibits hepatic gluconeogenesis. These properties raise important questions about fetal safety and potential influences on offspring developmental programming of metabolic disease. Both the placenta and fetus have metformin transporters and require high mitochondrial activity. Although metformin has favorable effects to reduce anti-angiogenic factors that may decrease preeclampsia, animal studies have demonstrated that prenatal metformin results in smaller birthweights, abnormal hepatic development, and adverse long-term outcomes in offspring later fed a western style diet. Findings from the Metformin in Gestational Diabetes (MiG) RCT found that nearly half of women treated with metformin failed and required supplemental insulin, rates of preterm birth were higher, and offspring had increased subcutaneous fat at age 2. These were similar to findings from a RCT in PCOS mothers. Two RCTs have used metformin in obese pregnancies. In neither trial was GDM or large-for-gestational age (LGA) reduced. Although metformin is beneficial in adults with diabetes or cancer, its anti-proliferative, nutrient restrictive, and respiratory suppressive effects could be responsible for its fetal growth effects rather than due to improved maternal glycemic control. Newer meta-analyses concur that it is impossible to determine the superiority of one oral antidiabetic agent over another due to study limitations, especially given that glyburide is typically dosed in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and a high rate of hypoglycemia. We concur with both the ADA and ACOG recommendations that insulin is the preferred agent and believe it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Carefully controlled studies that optimize oral medication dosing according to their pharmacokinetic properties, appropriately target medications based on individual patterns of hyperglycemia, and which follow the offspring long term for metabolic risk are gravely needed.