Oral Glucose-Lowering Agents Fall Short to Insulin for containing gestational diabetes Outcomes: JAMA
Researchers have determined that in comparison to insulin treatment, the use of a strategy of oral glucose-lowering agents with metformin and glyburide for the management of gestational diabetes mellitus (GDM) did not achieve the noninferiority threshold with regard to the risk for large-for-gestational-age (LGA) infants. A recent study was conducted by Doortje R. and colleagues which was published in the journal of JAMA Network.
GDM is a common complication of pregnancy associated with adverse outcomes such as LGA infants, maternal hypertension, and neonatal hypoglycemia. Insulin remains the standard treatment when dietary changes fail, but oral agents like metformin and glyburide are often explored as alternatives for convenience and patient preference. This study provides critical insights into the relative effectiveness of these approaches.
Participants in whom glycemic control was not adequate were randomly assigned to receive either oral glucose-lowering agents (n = 409) or insulin therapy (n = 411). Metformin was prescribed first at a dose of 500 mg daily and titrated up to 1000 mg twice daily or the highest tolerated dose. Glyburide was added as needed. The initiation of insulin was recommended for those who failed to achieve target glucose levels. Glycemic control targets were defined as fasting glucose >95 mg/dL, 1-hour postprandial glucose >140 mg/dL, or 2-hour postprandial glucose >120 mg/dL, as measured by self-monitoring.
The main outcome measure was the percentage of LGA infants, which was defined as birth weight >90th percentile for gestational age and sex. Secondary outcomes included maternal hypoglycemia, cesarean delivery, preeclampsia, neonatal hypoglycemia, hyperbilirubinemia, and NICU admissions.
Key findings
Among 820 participants, the mean age was 33.2 years (SD, 4.7 years).
In the oral therapy group, 79% (n = 320) maintained glycemic control without the use of insulin.
The LGA infants occurred in 23.9% (n = 97) in the oral therapy group and in 19.9% (n = 79) in the insulin group. Absolute risk difference was 4.0% (95% CI, -1.7% to 9.8%; p=0.09), which crossed the non inferiority margin of 8%.
Maternal hypoglycemia occurred in 20.9% participants with oral agents versus 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%).
Other secondary outcomes, such as cesarean delivery, preeclampsia, and NICU admissions, did not differ significantly between groups.
The study concluded that a sequential strategy of oral glucose-lowering agents was not noninferior to insulin in preventing LGA infants in women with GDM. Insulin remains the treatment of choice to achieve optimal perinatal outcomes. Oral agents remain an option for selected patients who cannot tolerate or access insulin and are monitored closely for glycemic control.
Reference:
Rademaker D, de Wit L, Duijnhoven RG, et al. Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial. JAMA. Published online January 06, 2025. doi:10.1001/jama.2024.23410
