No increased risk of malformations with metformin use in pregnancy with diabetes
Results from a Nordic study on pregnant women with type 2 diabetes indicate that use of the medication metformin does not lead to congenital malformations in the foetus.
The incidence of type 2 diabetes is increasing among women of childbearing age. The condition is characterised by high blood sugar levels, which can worsen during pregnancy and therefore require monitoring and treatment during pregnancy.
“High blood sugar increases the risk of malformations. That is why it is important that pregnant women with diabetes receive effective but safe treatment,” says Lars Kjerpeseth, researcher at the Department of Chronic Diseases at the Norwegian Institute of Public Health.
Traditionally, insulin has been used to regulate the blood sugar in pregnant women with type 2 diabetes. It is considered safe to use during pregnancy but requires injections. In recent years, it has become more common to prescribe metformin to this group. Metformin is more convenient for patients as it is taken in tablet form and has few side effects while effectively controlling blood sugar. Metformin is sold under the brand names Metformin or Glucophage at pharmacies.
“We wanted to find out if there is an increased risk of congenital malformations in the foetus if the mother uses metformin in the first trimester of pregnancy compared to insulin. We know that metformin, unlike insulin, is transferred to the foetus through the placenta,” continues Kjerpeseth.
Results of the study show that in 4.7 per cent of the pregnancies where the mother had used metformin, the child had a malformation, compared to 5.7 per cent of the pregnancies where insulin was used. Malformations usually occur in about 3 per cent of all newborns.
Cardiac malformations were the most common type of malformation, occurring in 2.0 per cent of pregnancies where the mother had used metformin and 2.1 per cent when insulin was used.
The researchers consider the results to be reassuring for patients and prescribers who want to use metformin during pregnancy.
“Malformations are often a concern when there is a need to use medications in pregnant women. Although metformin itself does not seem to increase the risk of malformations, we still see an increased incidence of malformations, both among those who use metformin and those who use insulin. This underscores the importance of pregnant women with type 2 diabetes receiving appropriate treatment to regulate their blood sugar,” says Kjerpeseth.
About the study and limitations
In the study, researchers from the Norwegian Institute of Public Health collaborated with researchers from several Nordic countries, using data from health registries in Norway, Sweden, Finland and Iceland.
Metformin and insulin have been compared in previous studies of pregnant women, but these studies were small and exposure in the first trimester has not been well studied.
“Congenital malformations are rare. Therefore, it is an advantage that we have been able to combine register data from several countries to achieve sufficient strength in our study to obtain robust results,” says Kjerpeseth.
The researchers had data on over 3.7 million women and children. Of these, 4023 births were to women with type 2 diabetes. Metformin was used by 3145 women (293 of these also used insulin) and 878 women used insulin alone.
The study has some limitations. Despite data from health registries in four countries, the researchers only had enough strength, meaning a sufficient number of births, to study the risk of all malformations and heart malformations combined, and not more specific malformations.
The study only included women who completed their pregnancy and gave birth. Therefore, the researchers could not study women who had an abortion or miscarriage after using metformin.
The study is part of a larger project at the Norwegian Institute of Public Health (NorPreSS/InPreSS) that examines the safety of medication use during pregnancy and is funded by NordForsk and the Research Council of Norway.
- Metformin Versus Insulin and Risk of Major Congenital Malformations in Pregnancies With Type 2 Diabetes: A Nordic Register-Based Cohort Study | Diabetes Care | American Diabetes Association (diabetesjournals.org)
- Diabetes Care On Air | Diabetes Care | American Diabetes Association (diabetesjournals.org) (episode 2. august 2023 (podcast)