Brick by Brick: Metformin for Gestational Diabetes Mellitus?

Jean-Luc Ardilouze; Masoud Mahdavian; Jean-Patrice Baillargeon

Disclosures

Expert Rev Endocrinol Metab. 2010;5(3):353-357. 

In This Article

Abstract and Introduction

Abstract

This paper reviews a case-control study, reported by Balani et al., comparing maternal and neonatal outcomes of women treated for gestational diabetes mellitus with either metformin or insulin. A cohort of 100 women treated with metformin alone, without insulin rescue, was compared with a retrospective cohort of 100 women treated with insulin. Results favored metformin. This paper discusses issues related to the safety and efficiency of metformin treatment during pregnancy, the attitudes of pregnant women toward treatment options, public health policy and the worldwide gestational diabetes mellitus epidemic, as well as the financial burden of therapy, particularly for developing countries. It also looks at the pathophysiology of gestational diabetes mellitus and the need for clinical trial assessment of combination oral-hypoglycemic therapy.

Introduction

Depending upon the population studied and diagnostic tests used, the prevalence of gestational diabetes mellitus (GDM) doubled over the past decade for all ethnicities, reaching 15–20% in high-risk populations,[1] as well as record high levels in large populations of the developing world (China, Africa and India).[2–4] Compounding this worrisome picture are the well-established accelerator hypothesis and fetal programming phenomenon,[5,6] otherwise known as the 'vicious cycle' of GDM,[7] according to which offspring of GDM become obese and diabetic earlier and faster than their parents.

It is thus pressing that both GDM screening and treatment become top universal priorities, especially since the benefits of treatment on pregnancy outcomes have been demonstrated, even for moderately hyperglycemic mothers. The most frequent short-term complications are indeed preventable[8,9] and, over the long term, treatment may decrease the prevalence of obesity and/or diabetes in offspring.[10]

Treatment of GDM is based on lifestyle changes through diet and exercise modifications. When these fail, insulin is the only pharmacological treatment widely recommended because of the fear of the potential adverse effects of alternative oral hypoglycemic agents (OHA), including fetal malformation and neonatal hypoglycemia.

However, several reasons explain why it is highly tempting to use OHA during pregnancy. First and foremost is the fact that for most pregnant women faced with pharmacotherapy,[11] taking insulin is not a suitable treatment option. Several well-read patients actually point out to their physicians evidence, found on the internet, with respect to the safety of OHA during pregnancy. Thus, women themselves are challenging medical recommendations. Another argument stems from recent reports demonstrating that treatment of GDM with glyburide[12] or metformin[11] is just as efficient as insulin. Nevertheless, insulin remains the ultimate therapy when the former fail to control glucose. Next, the economic argument, given the high cost of insulin therapy and the worldwide epidemic of GDM, suggests that the financial burden alone of GDM is expected to become unbearable, particularly for developing countries. The cost of GDM in the USA was some 636 million US dollars in 2007.[13] In India, where the population is four-times that in the USA, the cost of treatment of GDM with insulin is tenfold higher than with metformin.[14]

Therefore, studies on the relative safety of OHA treatment for the control of blood glucose during pregnancy are of the utmost importance. The report by Balani et al. sheds light on the relative efficacy and safety of metformin during pregnancy compared with insulin.[15] The cornerstone Metformin in Gestational Diabetes (MiG) prospective study of 741 women with mild GDM randomly assigned to metformin or insulin,[11] demonstrated no increase in perinatal complications compared with insulin, although spontaneous preterm births and preeclampsia were cause for concern with surprisingly high scores and trends. The Balani et al. study aims to balance out these findings.

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