Metformin in pregnancy: study shows no safety concerns
A large study has shown no safety issues of concern relating to the use of metformin during pregnancy. The licence for metformin now reflects that it can be considered for use during pregnancy and the periconceptional phase as an addition or an alternative to insulin, if clinically needed. This is consistent with current clinical guidance.
Risks of untreated diabetes in pregnancy
Uncontrolled hyperglycaemia in the time around conception (periconceptional phase) and during pregnancy is associated with increased risks to the baby and the patient. Good blood glucose control reduces the risk of congenital abnormalities, pregnancy loss, pregnancy-induced hypertension, preeclampsia, and perinatal mortality.
National guidelines in the UK already recommend metformin for use in diabetes during pregnancy and gestational diabetes if a healthcare professional feels it is appropriate (see guidelines from NICE and SIGN).
Review of new safety data
Following a European review of data from a non-interventional cohort study of population registries in Finland (the CLUE study), the product information for metformin is being updated to permit the use of metformin during pregnancy and the periconceptional phase as an addition or an alternative to insulin, if clinically needed. The Medicines for Women’s Health Expert Advisory Group of the Commission on Human Medicines has also reviewed the data from the study and agreed that the product information should be updated.
The study investigated immediate and longer-term effects of exposure to metformin in-utero on children born to patients with pre-existing type 2 diabetes, gestational diabetes, or polycystic ovary syndrome. The results of the study were reassuring, with no safety signals of concern identified for use of metformin in pregnancy relating either to those who were pregnant or their baby.[footnote 1]
Among secondary outcomes, similar rates of births that were small (low weight) for gestational age were observed with exposure to metformin and within the group of patients with untreated gestational diabetes. By contrast, an increased risk of small for gestational age was observed with exposure to metformin compared with insulin, which may relate to an overall increase in body weight due to use of insulin.
Updated advice
The advice in the Summary of Product Characteristics for metformin products is being updated. Corresponding changes are also being made to the Patient Information Leaflet. These changes have already been made to the brand-leader Glucophage.
Some fixed-dose combination products containing metformin contain other active substances that should be avoided during pregnancy. The product information for fixed-dose combination products containing metformin will be reviewed and advice on use in pregnancy updated if appropriate.
Advise patients with diabetes mellitus who are pregnant, think they may be pregnant, or are planning to have a baby to speak to their doctor. This is in case any changes are needed to their treatment or monitoring of their blood glucose.
Patents with type 1 diabetes mellitus must continue to take their insulin (as directed by a healthcare professional) in pregnancy.
This update to the product information reflects clinical practice and advice in current UK guidelines, including those from NICE and SIGN and resources from the BNF and UKTIS.
Report suspected adverse drug reactions in pregnancy
Report any suspected adverse drug reactions, including adverse pregnancy outcomes, following use of a medicine in pregnancy on a Yellow Card.
For more about the importance of reporting suspected adverse drug reactions associated with medicines in pregnancy, see Drug Safety Update, July 2018.
Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card App (Apple App Store and Google PlayStore).
Report suspected side effects to medicines, vaccines, medical device and test kit incidents used in coronavirus (COVID-19) testing and treatment using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app.
Post-publication note: March 2022
After publication we added advice for patients with type 1 diabetes following a query from a healthcare professional.
Article citation: Drug Safety Update volume 15, issue 8: March 2022: 3.
-
Brand KMG and others. Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study. BMJ Open Diabetes Res Care 2022; volume 10: e002363. ↩