Metformin is everywhere. Originally introduced in clinical practice as an antidiabetic
agent, its role as a therapeutic agent is expanding to include treatment of prediabetes
mellitus, gestational diabetes mellitus, and polycystic ovarian disease; more recently,
experimental studies and observations in randomized clinical trials suggest that metformin
could have a place in the treatment or prevention of preeclampsia. This article provides
a brief overview of the history of metformin in the treatment of diabetes mellitus
and reviews the results of metaanalyses of metformin in gestational diabetes mellitus
as well as the treatment of obese, non-diabetic, pregnant women to prevent macrosomia.
We highlight the results of a randomized clinical trial in which metformin administration
in early pregnancy did not reduce the frequency of large-for-gestational-age infants
(the primary endpoint) but did decrease the frequency of preeclampsia (a secondary
endpoint). The mechanisms by which metformin may prevent preeclampsia include a reduction
in the production of antiangiogenic factors (soluble vascular endothelial growth factor
receptor-1 and soluble endoglin) and the improvement of endothelial dysfunction, probably
through an effect on the mitochondria. Another potential mechanism whereby metformin
may play a role in the prevention of preeclampsia is its ability to modify cellular
homeostasis and energy disposition, mediated by rapamycin, a mechanistic target. Metformin
has a molecular weight of 129 Daltons and therefore readily crosses the placenta.
There is considerable evidence to suggest that this agent is safe during pregnancy.
New literature on the role of metformin as a chemotherapeutic adjuvant in the prevention
of cancer and in prolonging life and protecting against aging is reviewed briefly.
Herein, we discuss the mechanisms of action and potential benefits of metformin.
Key words
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Article info
Publication history
Published online: June 14, 2017
Accepted:
June 5,
2017
Received in revised form:
May 30,
2017
Received:
January 27,
2017
Footnotes
This work was supported, in part, by the Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C.
The authors report no conflict of interest.
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Published by Elsevier Inc.
