NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.
After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).
Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.
In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.
The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.
The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.
The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.
The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.
Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.
Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).
Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.
Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.
Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).
Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.