Is metformin ready for prime time in pregnancy? Probably not yet.

Metformin is one of the most commonly used drugs to treat type 2 diabetes and is safe and effective. Its main mechanism of action is thought to be the activation of AMP-activated protein kinase (AMPK) via inhibition of mitochondrial ATP generation. Recent use of metformin as an 'insulin sensitizer' in women with polycystic ovarian syndrome to increase fertility has been successful and resulted in the chance observation that continued use during pregnancy appeared to be safe. There are few studies of metformin in animal models of diabetic pregnancy. However, some data have implicated fetal AMPK activation in neural tube defects. While a recent report suggests that metformin may not activate fetal AMPK, which is reassuring, studies in pregnant woman with gestational diabetes and type 2 diabetes, which are ongoing, require completion before we can conclude that its use in pregnancy is safe. Furthermore, follow-up of the offspring will be critical to determine whether such treatment decreases or increases the development of obesity and diabetes.