Metformin vs insulin in the management of gestational diabetes: A systematic review and meta-analysis

Abstract

Objective

To evaluate the effectiveness of metformin compared with insulin in achieving glycemic control and investigate the maternal and neonatal outcomes in gestational diabetes mellitus.

Methods

We searched four electronic databases from inception through December 2012. Terms for Gestational diabetes/gestational diabetes mellitus/diabetes pregnancy AND/OR Metformin/hypoglycemic drugs/Hypoglycemic Agents/Antidiabetic Medications were used in the search. Two investigators independently reviewed titles and abstracts, performed data abstraction on full articles, and assessed study quality. Meanwhile, manual search of other resources and the search on Google Scholar were also carried out to identify more related articles .Rev Man 5.0 was used to analyze the data.

Results

Six randomized clinical trials involving 1420 subjects were included. The current limited data suggested that using metformin in gestational diabetes subjects did not significantly increase adverse maternal outcomes and neonatal outcomes, also with less weight gain and neonatal hypoglycemia, but a higher incidence of premature birth.

Conclusions

Metformin will not increase the incidence of adverse maternal outcomes and neonatal outcomes.

Introduction

GDM has been defined as any degree of glucose intolerance with onset or first recognition during pregnancy [1].GDM is associated with an increased risk of complications for both the mother and the baby during pregnancy and birth. The prevalence of GDM varies widely depending on the population studied, but the overall estimated prevalence in the United States is 2% to 10% [2]. Treatment for GDM could reduce adverse pregnancy outcomes [3]. Historically, insulin has been the therapeutic agent of choice for controlling hyperglycemia in women with GDM who could not be controlled by medical nutrition therapy and physical activity. However, difficulty in medication administration with multiple daily injections, potential for hypoglycemia, and increase in appetite and weight make this therapeutic option difficult for many pregnant women [4].

Using oral diabetes medication in women with GDM has accumulated more clinical evidence even though they have not been formally approved by the U.S. Food and Drug Administration for this indication [5].

Metformin is one such medication and studies have shown different outcomes with metformin in women with GDM. One study evaluating the efficacy and safety of metformin treatment in women with pregestational and gestational diabetes raised concerns about a higher perinatal mortality and a higher rate of preeclampsia [6]. However, a recent large randomized controlled trial which compared metformin with insulin in the treatment of gestational diabetes (MiG trial) suggested that metformin, alone or with supplemental insulin, was an effective and safe treatment option for women with gestational diabetes [7].

A recent systematic review concluded that oral agents are suitable for managing gestational diabetes because they achieved good glycemic control and maternal and perinatal outcomes comparable with insulin, but the meta-analysis included only two trials of metformin, and did not separate metformin and glyburide [8]. Since the use of metformin in pregnant women remains controversial, we conducted a systematic review and meta-analysis of randomized controlled trials of metformin with the aim of comparing the effects and safety of metformin in gestational diabetes mellitus with insulin.