Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

Abstract

Importance:

Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes.

Objective:

To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes.

Design, Settings, and Participants:

The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation.

Interventions:

Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations.

Main Outcomes and Measures:

The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval.

Results:

Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19).

Conclusion and Relevance:

This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment.

Trial Registration:

clinicaltrials.gov Identifier: NCT01731431.

• Authors: Marie-Victoire Sénat, Helene Affres, Alexandra Letourneau, Magali Coustols-Valat, Marie Cazaubiel, Helene Legardeur, Julie Fort Jacquier, Nathalie Bourcigaux, Emmanuel Simon, Anne Rod, Isabelle Héron, Virginie Castera, Loic Sentilhes, Florence Bretelle, Catherine Rolland, Mathieu Morin, Philippe Deruelle, Celine De Carne, François Maillot, Gael Beucher, Eric Verspyck, Raoul Desbriere, Sandrine Laboureau, Delphine Mitanchez, Jean Bouyer, Groupe de Recherche en Obstétrique et Gynécologie (GROG)
• Journal: JAMA (JAMA) Vol. 319 Issue 17 Pg. 1773-1780 (05 01 2018) ISSN: 1538-3598 [Electronic] United States
• PMID: 29715355 (Publication Type: Comparative Study, Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Glyburide

Topics

• Administration, Oral
• Adult
• Blood Glucose (analysis)
• Diabetes, Gestational (blood, drug therapy)
• Female
• Fetal Macrosomia (etiology, prevention & control)
• Glyburide (adverse effects, therapeutic use)
• Humans
• Hyperbilirubinemia (etiology, prevention & control)
• Hypoglycemia (chemically induced, etiology, prevention & control)
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Infant, Newborn
• Infant, Newborn, Diseases (epidemiology)
• Injections, Subcutaneous
• Insulin (adverse effects, therapeutic use)
• Pregnancy
• Pregnancy Outcome