Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.

Summary

In this multicenter noninferiority RCT (n=820), a sequential oral strategy (metformin with add-on glyburide, then insulin if needed) did not meet noninferiority versus insulin for preventing large-for-gestational-age infants (23.9% vs 19.9%). Maternal hypoglycemia occurred more frequently with oral agents (20.9% vs 10.9%), while other maternal and neonatal outcomes were similar.

Key Findings

• Primary outcome: LGA infants 23.9% (oral) vs 19.9% (insulin); noninferiority not met (ARD 4.0%, 95% CI -1.7% to 9.8%).
• 79% of participants randomized to oral agents achieved glycemic control without insulin.
• Maternal hypoglycemia was higher with oral agents (20.9%) vs insulin (10.9%).
• Other secondary outcomes (cesarean, preeclampsia, neonatal outcomes) were similar between groups.

Clinical Implications

Insulin should remain the standard when pharmacotherapy is needed to minimize LGA risk; sequential oral therapy may be considered when insulin is not acceptable, with counseling about increased maternal hypoglycemia and close monitoring.

Limitations

• Open-label design may introduce performance and detection bias.
• Sequential algorithm included glyburide rescue; generalizability may vary by practice patterns and populations.

Future Directions

Head-to-head blinded RCTs of different oral strategies versus insulin, stratified by baseline risk; evaluation of long-term offspring outcomes and maternal cardiometabolic effects.