Advice on prescribing metformin prophylactically
Asked after his presentation whether women with a history of GDM and either an elevated fasting plasma glucose value or an elevated 2-hour oral glucose tolerance test (GTT) value – or neither of the two – would benefit from taking metformin, Dr. Ratner said that “we’re stuck with inclusion criteria of the DPP, in which they had to meet both criteria ... What I’d say, though, is that not everyone with a history of GDM needs to be on metformin prophylactically. But [for women who have] prediabetes as defined by the ADA, the cost-benefit analysis points toward metformin.”
And with respect to early initiation and long-term use of the drug, “I would have absolutely no qualms about medicating a 25-year-old who had developed GDM and who in the postpartum period has prediabetes,” Dr. Ratner said during an open discussion. “She’s actually at the highest risk for developing type 2 very early.”
Kim Boggess, MD, who also presented on long-term use of metformin after GDM, said in the discussion period that she is often quick to recommend metformin therapy to her patients who have an elevated fasting plasma glucose value in the postpartum period, even when a 75-g oral GTT has not yet been performed. (The ADA and the American College of Obstetricians and Gynecologists recommend completion of an oral GTT at 4-12 weeks postpartum after GDM.)
“I start them [on metformin] especially if they’ve had a cesarean section. Even 2, 3, 4 weeks of profound hyperglycemia could have potentially deleterious effects,” said Dr. Boggess, professor and maternal-fetal medicine program director at the University of North Carolina, Chapel Hill. “If someone comes in [shortly after] and looks like they have pristine control, then it might be worth stopping the metformin for 3-5 days (and retesting).”
Dr. Ratner said that, in this clinical scenario, he would first ensure that the fasting glucose value “is a true fasting glucose” and “if it’s substantially elevated – I’m talking 100, 105, 110 mg/dL – I’d start metformin, and I’m not even sure I’d do the GTT.” But, he advised, “if you’re going to do the GTT, I’d stop the metformin the day before.”
In her presentation, Dr. Boggess pointed out that metformin wasn’t shown to be superior to lifestyle interventions in the DPP for preventing progression to type 2 DM, and that some women are more motivated for intensive lifestyle change than others. The ADA recommends, in fact, that either metformin or lifestyle interventions be prescribed to women with a history of GDM who are found to have prediabetes.
Dr. Kim Boggess
There are no data to support the use of metformin either during or after pregnancy to improve weight loss or reduce weight retention following pregnancy, but at least several studies have shown that lifestyle interventions are effective, she noted.
What is needed, Dr. Boggess said, are more data on the effects of metformin on cardiovascular disease risk, as well as larger studies of metformin in the postpartum period “to help us determine the best dose.” Some research on metformin use in the postpartum period has reported gastrointestinal side effects and dissatisfaction, she noted.
Dr. Ratner said that metformin’s main drawback is the need for occasional testing of B12 levels. Regarding weight loss and what was observed in the DPP, he said, women with a history of GDM who were randomized to intensive lifestyle interventions did not lose as much weight as women without a history of GDM.
Women who entered the DPP with a GDM history, he noted in his presentation, were essentially a “cohort of survivors.” They had an average age of 43 (compared with 52 years in the parous women without GDM) and a mean interval from the index GDM pregnancy of 11 years, which means that women with the highest risk of diabetes conversion were excluded, Dr. Ratner said.
Age was the only significantly different baseline characteristic between parous women with and without GDM, he noted. Women with a history of GDM who were randomized to placebo had a 71% higher incidence of diabetes than women without such a history – a striking natural history, Dr. Ratner said.
He and Dr. Boggess each reported that they have no financial or other interests that pose a conflict of interest.