HAMBURG –
Overall, the trial’s primary outcome, a composite of insulin initiation or a fasting glucose level ≥ 5.1 mmol/L (92 mg/dL) at gestation weeks 32 or 38, did not differ between women with gestational diabetes randomly assigned to either placebo or metformin. However, women taking metformin were significantly less likely to require insulin and had significantly lower fasting blood glucose levels at weeks 32 and 38.
“With a composite outcome it’s more difficult to find a positive result ... So, although the primary composite outcome was not positive, the components of the primary outcome that are clinically meaningful were positive,” lead study author Fidelma Dunne, PhD, professor and endocrine consultant at the University of Galway, Ireland, said in an interview.
There were no differences in maternal or neonatal morbidities, but there was a nonsignificant increase in small for gestational age (SGA), a finding that has been seen in some but not all previous studies of metformin use in gestational diabetes.
Dr. Dunne presented the findings on Oct. 3 at the annual meeting of the European Association for the Study of Diabetes. The results were simultaneously published in JAMA.
Current recommendations from the United Kingdom’s National Institute for Health and Care Excellence say metformin is a suitable first-line therapy for gestational diabetes. However, both the American Diabetes Association and the Society of Maternal-Fetal Medicine do not, particularly for pregnancies with hypertension or preeclampsia or in those who are at risk for intrauterine growth restriction.
“Gestational diabetes is now reaching epidemic proportions. And of course, the vast majority of these women are in low- and middle-income countries where insulin might not be available, or the storage may not allow it to be used effectively. If you have a medication that in the majority of women is safe and effective it may actually help a lot of women in [those regions],” Dr. Dunne said.
Moreover, she noted, “women with gestational diabetes are testing their sugar with finger pricks four to seven times per day and we ask them to take insulin one to four times a day. So if you can relieve any of that pain related to treatment of their condition than that is a benefit for the women as well.”
Asked to comment, Katrien Benhalima, MD, PhD, of University Hospital Gasthuisberg, KU Leuven, Belgium, said, “I think it’s an interesting study because they investigated something novel, to initiate immediately metformin or placebo. Normally what we do with gestational diabetes is once we get the diagnosis, we treat them with lifestyle, and if that’s insufficient then we start with medical therapy. So this is a novel approach.”
She also agreed with Dr. Dunne that the lack of significance for the primary outcome “isn’t an issue of power but it is a composite outcome. If you look at the individual outcomes, as can be expected, the women taking metformin had less need for insulin treatment.”
But, Dr. Benhalima said, the study still leaves open the SGA issue. “It wasn’t significant, but it’s still something we are worried about in the sense that we feel we need more data, especially in the long-term for the offspring health ... You really need to follow them for 10 years or longer to see an effect.”
So for now, Dr. Benhalima said that she wouldn’t use metformin as a first-line treatment for gestational diabetes. “Normally if lifestyle isn’t enough we will still start insulin ... Another issue is why would you offer everybody medical treatment when pregnancy outcomes can be met with lifestyle alone?”
Then again, she added, “of course metformin is easier than an injection. Treatment satisfaction is improved, and the cost is less.”