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Metformin Can Delay or Prevent Diabetes in Women Who Had Gestational Diabetes 

Following a healthy diet or taking metformin may help to delay or prevent diabetes in women with a history of gestational diabetes mellitus (GDM) and impaired glucose tolerance, according to the results of a randomized controlled clinical trial.

"A past history of [GDM] confers a very high risk of post-partum development of diabetes, particularly type 2 diabetes," write Robert E. Ratner, from Medstar Research Institute in Hyattsville, Maryland, and colleagues from the Diabetes Prevention Program (DPP) Research Group. "The DPP sought to identify individuals with impaired glucose tolerance (IGT) and intervene in an effort to prevent or delay their progression to diabetes. This analysis examines the differences between women enrolled in DPP with and without a reported history of GDM."

This National Institutes of Health–sponsored trial was performed at 27 centers, including academic and Indian Health Services sites. The DPP enrolled 2190 women who were randomly assigned either to standard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention and who provided information for past history of GDM. This analysis compares 350 women who had a past history of GDM with 1416 women who had a previous live birth but no history of GDM.

The main endpoint was the time to development of diabetes, identified by semiannual fasting plasma glucose and annual oral glucose tolerance testing. Other endpoints were evaluations of insulin secretion and insulin sensitivity.

Despite similar glucose levels at study enrollment, women with a history of GDM who were randomly assigned to placebo had a crude incidence rate of diabetes that was 71% higher than that of women who had no history of GDM. Among women with a positive history for GDM, both intensive lifestyle and metformin therapy were associated with a reduction in the incidence of diabetes of approximately 50% vs the placebo group, whereas this reduction was 49% and 14%, respectively, in parous women without GDM.

"These data suggest that metformin may be more effective in women with a GDM history as compared to those without," the study authors write. "Progression to diabetes is more common in women with a history of GDM compared to those without GDM history despite equivalent degrees of IGT at baseline. Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM."

A previous study, published in the February 7, 2002, issue of the New England Journal of Medicine, demonstrated that metformin could reduce the risk for incident type 2 diabetes among patients with impaired glucose tolerance, although intensive lifestyle intervention was even more effective in preventing diabetes. This research examined the same DPP cohort evaluated in the current study. The DPP randomly assigned participants to treatment with placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7% weight loss and at least 150 minutes of physical activity per week. After nearly 3 years of follow-up, the lifestyle intervention and metformin respectively reduced the incidence of diabetes by 58% and 31% compared with placebo.

The current article examines women from the DPP to determine the relative benefits of metformin and intensive lifestyle according to their history of GDM.
Practice Pearls:

  • The DPP demonstrated that both metformin and intensive lifestyle could reduce the risk for incident diabetes among patients with impaired glucose tolerance. Intensive lifestyle was superior to metformin in this outcome.
  • In the current study, intensive lifestyle and metformin reduced the risk for incident diabetes to a similar degree among women with a history of GDM, but metformin was less effective than lifestyle change among women who did not have a history of GDM.

J Clin Endocrinol Metab. Published online September 30, 2008.

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