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.