Globally, the number of women of reproductive age who have diabetes is increasing. This means more women than ever are having to manage their condition through pregnancy. Added to which, approximately 10% of women will develop a form of glucose intolerance, known as Gestational Diabetes Mellitus (GDM), during pregnancy, which if left untreated can cause adverse health outcomes to both the mother and the unborn child.
The main options for managing diabetes are via nutrition, insulin injections, or oral anti-diabetic agents (OAAs). Nutrition would be the preferred choice if success was guaranteed. However, dietary changes are only thought to help about 50% of women with GDM and if a rapid improvement is not seen, your doctor will probably encourage additional medication to help control your blood sugar levels and minimise stress to your unborn child.
Insulin is the standard treatment for diabetes. It has unparalleled safety and efficacy and is favoured by many doctors for the treatment of diabetes during pregnancy as it does not cross the placenta, meaning there is no foetal exposure to the drug. The downside to this treatment is that it is delivered via injection (syringe, pen or pump), so there is a risk of low compliance.
The main OAAs in use are metformin and glyburide. Glyburide increases the release of insulin from the pancreas. In studies investigating its effectiveness compared to metformin, it has performed less well, with expectant mothers gaining more weight and giving birth to heavier infants. As such, metformin is often the drug of choice for treating diabetes during pregnancy. Metformin works by reducing the amount of glucose produced by the liver. It also enhances insulin sensitivity, thus is often given as an adjunct to insulin therapy. Clinical studies have revealed that diabetic women who used metformin during pregnancy gave birth to babies with a lower birth weight and these infants had a reduced risk of hypoglycaemia. However, questions do still remain over the long-term safety of the drug and guidelines for its usage differ between countries.
The UK National Institute for Health and Clinical Excellence (NICE) and the International Federation of Gynecology and Obstetrics (FIGO) consider it an appropriate treatment option; whereas the American Congress of Obstetricians and Gynecologists (ACOG), the American Diabetes Association (ADA), and the International Diabetes Federation (IDF) suggest that there is insufficient evidence at presence to prescribe it routinely. It has been classified as Category B by the American Food and Drug Administration (FDA), meaning animal studies have not revealed any risk, but there remains a shortage of human studies. In fact, the FDA has yet to approve any OAA for use in pregnancy.
Certainly, there are unknowns with regards to metformin; not least, a lack of awareness regarding any long term effects on child development. Metformin does cross the placenta, resulting in significant foetal exposure. The concern is that this exposure could cause defective programming events and thus, affect the child years later. In the short-term, metformin does not increase the risk of birth defects, miscarriage, stillbirth, or premature delivery. It is well tolerated and is regularly prescribed to restore ovulatory menstrual cycles in women with polycystic ovary syndrome (PCOS).
Why timing is important
The first trimester is considered to be the most critical time for minimising foetal exposure to xenobiotics, including therapeutic medications. This is when the baby’s organs are being formed and risk of damage is highest. However, many women with PCOS take metformin prior to conception and during the early weeks of pregnancy and there is no evidence of increased birth defects as a result.
Incidentally, most women who develop GDM will be diagnosed at approximately weeks 24-28 of pregnancy, which is well past the critical first trimester. Those that are diagnosed earlier are at greater risk of foetal malformations and pregnancy complications as a direct result of their condition. In these instances, the risks to the mother and baby of leaving their condition untreated far outweigh the risks of taking medication during the first trimester.
When considering how best to manage your diabetes during pregnancy, the main thing to bear in mind is minimising adverse outcomes for both you and your baby. In terms of health outcomes, OAAs seem to be as effective as insulin, suggesting they are viable alternative. Those preliminary studies that suggested a high incidence of adverse outcomes following metformin use have since been questioned for their validity and scientific soundness.
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- Kalra, B, et al. “Use of Oral Anti-Diabetic Agents in Pregnancy: A Pragmatic Approach.” North American Journal of Medical Sciences, vol. 7, no. 1, Jan. 2015, pp. 6–12., doi:10.4103/1947-2714.150081.
- “Metformin.” Bumps (Best Use of Medicines in Pregnancy), UK Teratology Information Service, www.medicinesinpregnancy.org/Medicine–pregnancy/Metformin/.
- Polasek, T M, et al. “Metformin Treatment of Type 2 Diabetes Mellitus in Pregnancy: Update on Safety and Efficacy.” Therapeutic Advances in Drug Safety, vol. 9, no. 6, June 2018, pp. 287–295., doi:10.1177/2042098618769831.
- “Prenatal Care.” American Diabetes Association, www.diabetes.org/living-with-diabetes/complications/pregnancy/prenatal-care.html.
- Priya, G, and S Kalra. “Metformin in the Management of Diabetes during Pregnancy and Lactation.” Drugs in Context, vol. 7, 15 June 2018, p. 212523., doi:10.7573/dic.212523.