WASHINGTON – Metformin’s role in preventing or delaying the onset of type 2 diabetes in women with a history of gestational diabetes mellitus has been firmly established by the Diabetes Prevention Program (DPP) trial – most recently, by 15-year follow-up data reported this year – and the drug should be front and center for clinicians who hope to stave off the “remarkable” incidence of type 2 diabetes after GDM,, maintained at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
The DPP included “the single largest population of women with a history of GDM that’s been looked at in a randomized controlled trial,” and considering its multiethnic population, the trial offers a reliable representative sample to ponder today when evaluating long-term use of metformin after GDM, said Dr. Ratner, a principal investigator of the National Institutes of Health–sponsored DPP and the DPP Outcomes Study and a former chief scientific & medical officer for the American Diabetes Association.
The drug stacked up equally to lifestyle interventions among DPP participants who had a history of GDM, but it’s important to appreciate that these interventions were intensive and that metformin is inexpensive, well tolerated, and “has a long safety record,” he said.
Results of follow-up out to 15 years
Of the more than 3,000 men and women enrolled in the landmark DPP, conducted during 1996-2001, 350 were women with a documented history of GDM and over 1,400 were women who had deliveries but no history of GDM. All participants had impaired glucose tolerance – defined for the trial as having both a fasting plasma glucose value of 95-125 mg/dL and a 2-hour value of 140-199 mg/dL after a 75-g glucose load – and were randomized to placebo, metformin, or intensive lifestyle intervention.
Metformin therapy reduced the incidence of diabetes by approximately 50% in women with a history of GDM, compared with the placebo group – as did lifestyle – over 3 years. The number needed to treat to prevent one case of diabetes was five. Women without a history of GDM, on the other hand, saw only a 14% reduction with metformin when compared with placebo (and a 49% reduction with lifestyle).
“In women with a history of GDM ... one pill twice a day for $4 a month worked as well as intensive lifestyle [change],” Dr. Ratner said, referring to the initial GDM-specific analysis of DPP data published in 2008 ().
In a 10-year postrandomization follow-up, published in 2015, both metformin and lifestyle continued to be equally effective for the GDM group, reducing the progression to diabetes by 40% and 35%, respectively (). The number needed to treat to prevent one case of diabetes was seven. (Among women without a history of GDM, metformin did not reduce progression to diabetes.)
A recent DPP Outcomes Study analysis of metformin’s impact on diabetes prevention at 15 years, moreover, showed a 41% risk reduction among women with a history of GDM (