Abstract
(BMJ. 2018;361:k2477) Metformin is a commonly used drug for the treatment of type 2 diabetes. It has also been used in women with polycystic ovary syndrome to improve insulin sensitivity. Since 2008 the drug has been recommended for use in pregnancy in the United Kingdom for women with type 2 diabetes or gestational diabetes. However, its use in pregnancy remains controversial as it affects stem cell function and concerns have been raised about potential teratogenic effects. Animal studies and meta-analyses in humans have not provided evidence of increased risk for congenital anomalies. However, one cohort study involving 392 women did report an increased risk of congenital anomalies in women taking metformin for diabetes, but no increased risk was found when the drug was being taken for other indications. This led those investigators to conclude the increased risk of anomalies was related to the patients’ diabetes and not the exposure to metformin. In contrast, it has also been suggested that metformin could decrease the risk of congenital anomalies in parturients with diabetes by improving glycemic control. This current study aimed to investigate the effect of first trimester metformin exposure on all or specific congenital anomalies by using a European database.
Highlights
Metformin is an oral blood glucose lowering drug that has been used in the treatment of type 2 diabetes since the 1950s.1 Despite reservations about its use in pregnancy, metformin has been recommended for use in pregnancy in the UK since 2008 in women with gestational diabetes and in type 2 diabetes when the likely benefits outweigh the potential for harm.[2 3]
Metformin affects stem cell function and has been shown to cross the human placenta at term, exposing the fetus to concentrations approaching those in the maternal circulation Limited evidence from three meta-analyses and a cohort study suggests that the rate of all major congenital anomalies combined is not significantly increased after exposure to metformin As teratogens tend to increase the risk of specific, rather than all, congenital anomalies, an increased risk of specific congenital anomalies after first trimester metformin exposure cannot be ruled out
No evidence was found for an increased risk of all non-genetic congenital anomalies combined following exposure to metformin during the first trimester, and the one significant association was no more than would be expected by chance
Summary
Metformin is an oral blood glucose lowering drug that has been used in the treatment of type 2 diabetes since the 1950s.1 Despite reservations about its use in pregnancy, metformin has been recommended for use in pregnancy in the UK since 2008 in women with gestational diabetes and in type 2 diabetes when the likely benefits outweigh the potential for harm.[2 3]. Metformin is an oral blood glucose lowering drug that has been used in the treatment of type 2 diabetes since the 1950s.1. Metformin is prescribed in polycystic ovary syndrome, in which it improves insulin sensitivity, may aid weight reduction, and helps to normalise the menstrual cycle (increasing the rate of spontaneous ovulation).[6] Exposure to metformin in early pregnancy among women undergoing treatment for polycystic ovary syndrome may occur. The use of metformin to prevent diabetes in pre-diabetic populations, as a cancer treatment,[7 8] and as a weight loss medication for non-diabetic obesity is of interest.[9 10] Expansion of indications for metformin use will increase the risk of unintentional exposures during pregnancy
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