Currently, the multisite MOMPOD trial (Medical Optimization of Management of T2DM Complicating Pregnancy) is randomizing 950 women to insulin plus 1,000 mg metformin twice daily or insulin plus placebo. The primary outcome of the trial is a composite of pregnancy loss, preterm birth, birth injury, neonatal hypoglycemia, or hyperbilirubinemia. Infant fat mass (within 72 hours of birth) is a secondary outcome, along with maternal safety and maternal side effects.
The MiTy (Metformin in Women with T2DM in Pregnancy) trial in Canada, with similar randomization arms and outcomes measures, is completed and undergoing analysis. “Hopefully we’ll [soon] be able to say whether the addition of adjuvant metformin to insulin to treat type 2 diabetes brings the perinatal adverse outcome rate down from 30%,” said Dr. Boggess.
Metformin is the recommended first-line agent for type 2 diabetes in nonpregnant adults. But during pregnancy, insulin, which does not cross the placenta, is the preferred agent, according to recommendations of the American Diabetes Association and the American College of Obstetricians and Gynecologists, she noted. Lingering in the background is the fact that the long-term effects of in utero metformin exposure on offspring – and of exposure to any oral hypoglycemic agent – are unknown, she said*
A majority of the adverse pregnancy outcomes that occur in the context of type 2 diabetes involve macrosomia. “It’s a big deal,” Dr. Boggess said, that results in numerous maternal and infant risks and complications. “We also know that the in utero environment that contributes to, or causes, macrosomia predisposes to childhood obesity and obesity later on.”
Diabetes is the “leading risk factor” for adverse pregnancy outcomes today, said E. Albert Reece, MD, PhD, MBA, executive vice president for medical affairs at the University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers distinguished professor and dean of the University of Maryland School of Medicine. In the United States, 11% of women aged 20 years and older have diabetes, and the disease affects more than 1% of all pregnancies, he said.
The MOMPOD trial is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Boggess reported no conflicts of interest.
* This article was updated 1/2/2020.