Insulin optimal for gestational diabetes management vs. oral therapies
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Key takeaways:
- The proportion of large for gestational age infants was higher with oral agents vs. insulin therapy for women with gestational diabetes.
- Maternal hypoglycemia was higher in the oral agents vs. insulin groups.
Treatment with metformin plus glyburide was not noninferior to insulin alone in preventing large for gestational age infants born from pregnant women with gestational diabetes, according to trial results published in JAMA.
“Treatment satisfaction is higher for metformin than insulin for gestational diabetes, although supplemental insulin is frequently needed, and early treatment with metformin does not reduce insulin initiation,” Doortje Rademaker, MD, a doctoral student in the department of obstetrics and gynecology at Amsterdam University Medical Center and the Amsterdam Reproduction and Development Research Institute in the Netherlands, and colleagues wrote. “Glyburide monotherapy has demonstrated clinical efficacy comparable with insulin, with maternal hypoglycemia as the most frequently reported adverse effect. A sequential combination of glucose-lowering agents could reduce the need for supplemental insulin while potentially increasing patient satisfaction and reducing costs.”
Comparing insulin, oral therapies
Rademaker and colleagues conducted a randomized, open-label noninferiority trial with 820 women (mean age, 33.2 years) with singleton pregnancies between 16 and 34 weeks’ gestation from 25 Dutch centers from June 2016 to November 2022. All participants had gestational diabetes with insufficient glycemic control after 2 weeks of dietary changes. Researchers randomly assigned participants to metformin at a starting dose of 500 mg once daily increasing every 3 days to 1,000 mg twice daily or the highest tolerated level (n = 409) or insulin, prescribed according to local practice (n = 411).
Researchers added glyburide to metformin and insulin was substituted for glyburide if needed to achieve glucose targets.
Primary outcome was the between-group difference in the percentage of large for gestational age infants. Secondary outcomes included maternal hypoglycemia, cesarean birth, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm birth, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia and NICU admission.
Overall, 79% of pregnant women in the metformin or metformin plus glyburide groups maintained glycemic control without insulin treatment. In addition, 23.9% of pregnancies in the metformin or metformin plus glyburide group resulted in large for gestational age infants compared with 19.9% in the insulin group.
One-fifth (20.9%) of women in the metformin or metformin plus glyburide groups and 10.9% of women in the insulin group experienced maternal hypoglycemia. All other secondary outcomes were not different between groups.
Researchers observed a higher proportion of women in the metformin or metformin plus glyburide groups who reported adverse events compared with women in the insulin group (78% vs. 56%). The most reported adverse effects for both groups were nausea (39% and 13%), diarrhea (39% and 5%), headaches (20% and 13%) and vomiting (15% and 1.7%).
Insulin preferred for glycemic management
“Outside of pregnancy, noninsulin medications are commonly used alone or in combination to treat diabetes,” Camille E. Powe, MD, endocrinologist and co-director of the Diabetes in Pregnancy Program in the division of endocrinology in the department of medicine and the department of obstetrics and gynecology at Massachusetts General Hospital at Harvard Medical School, wrote in an accompanying editorial. “In pregnancy glycemic management, insulin is queen.”
Powe noted that these findings support the continued importance of insulin as the preferred pharmacotherapy for gestational diabetes vs. a sequential oral medication strategy that includes glyburide.
“Given the cost, complexity and burden associated with insulin therapy, Rademaker et al have contributed a valiant, yet ultimately unsuccessful, attempt to establish an alternative oral pharmacotherapeutic strategy for the thousands of pregnancy individuals diagnosed with gestational diabetes each year,” Powe wrote. “For now, insulin reigns supreme.”