A narrative review of metformin in pregnancy: Navigating benefit and uncertainty

Metformin is well-established as a treatment for type 2 diabetes in non-pregnant individuals. The low cost, acceptability and broad tolerability of metformin have also made it an attractive option for research into the treatment of other conditions associated with insulin resistance. Despite almost 50 years of clinical experience with the use of metformin to treat diabetes in pregnancy, many questions remain regarding its precise effectiveness in different maternal subgroups, as well as potential short-term and long-term effects on the offspring. In this narrative review, we present the current evidence for the use of metformin during pregnancy in various maternal subgroups, including women living with overweight and obesity, women at risk of gestational diabetes, women diagnosed with gestational diabetes and women with pregestational diabetes, including type 2 diabetes. Our specific focus is on the impact of metformin on short-term maternal, fetal and neonatal outcomes. We also consider the evidence for other emerging indications for metformin in pregnancy, such as the prevention and management of pre-eclampsia. PLAIN LANGUAGE SUMMARY: This article looks at research on how metformin use in pregnancy affects mothers and newborns in the short term. Doctors have prescribed metformin since the 1970s for the treatment of diabetes in pregnancy. Despite years of use, there are still questions about how safe and effective metformin is for mothers and their children. Metformin taken during pregnancy moves through the placenta into the foetus's bloodstream. The short-term and long-term effects of metformin on offspring need careful attention. The studies that have looked at the link between metformin use and birth defects have not found any strong link between taking metformin in pregnancy and birth defects, however close attention will continue to be paid in this area. Some large studies have examined the use of metformin in pregnant women who do not have diabetes, but who do live with overweight or obesity. The studies are difficult to compare. Some, but not all, of these studies have shown less weight gain for the mother if metformin is taken by these women during pregnancy. Other large studies have looked at whether metformin can prevent gestational diabetes. The results are mostly disappointing. They suggest that metformin does not stop gestational diabetes from developing. However, the participants in these studies were mostly from white backgrounds and metformin may help prevent gestational diabetes in women of different ethnic backgrounds. However, more research is needed. Metformin has been widely studied as an alternative to insulin for the treatment of gestational diabetes. Because different countries diagnose and treat GDM differently, this makes comparing study results difficult. Women with gestational diabetes seem to gain less weight during pregnancy if they use metformin rather than insulin. Using metformin instead of insulin may result in lower average birth weights for babies from these pregnancies. Also, the use of metformin may lead to fewer babies being born abnormally large. Similarly, large trials have examined the use of metformin in pregnant women who are living with type 2 diabetes. These studies show that metformin can lower a mother's insulin needs. It can also help control weight gain and reduce the risk of having a large baby. One study found that metformin use in women living with Type 2 diabetes might increase the risk of having smaller babies. This was especially true if the mother had high blood pressure or kidney disease. This finding requires further investigation. Metformin might help prevent pre-eclampsia, but this is still unclear. Research is ongoing into a potential role for metformin in the treatment of pre-eclampsia. In conclusion, metformin has been studied in many groups of pregnant women. Women with gestational diabetes or type 2 diabetes may see benefits like less weight gain and better blood sugar/glucose control. Current evidence suggests that metformin shouldn't be used if there are foetal growth issues. It is also not recommended for mothers with high blood pressure or kidney disease. Future studies might find specific groups of pregnant women who would benefit the most from metformin.