[Skip to Content]
[Skip to Content Landing]
Original Investigation
May 1, 2018

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational DiabetesA Randomized Clinical Trial

Author Affiliations
  • 1Assistance Publique–Hôpitaux de Paris, Department of Gynecology-Obstetrics, Bicêtre Hospital, Le Kremlin-Bicêtre, France
  • 2University of Paris-Sud, University of Medicine Paris-Saclay, Le Kremlin-Bicêtre, France
  • 3Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, Université de Versailles Saint-Quentin-en-Yvelines, INSERM, Villejuif, France
  • 4Assistance Publique–Hôpitaux de Paris, Department of Reproductive Endocrinology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
  • 5Assistance Publique–Hôpitaux de Paris, Department of Gynecology-Obstetrics, Béclère Hospital, Clamart, France
  • 6Department of Endocrinology-Obstetrics, Toulouse University Hospital, Toulouse, France
  • 7Department of Endocrinology, Lille University Hospital EA 4489–Environnement Périnatal et Santé, Lille, France
  • 8Assistance Publique–Hôpitaux de Paris, Department of Gynecology and Obstetrics, Hôpital Louis Mourier, Colombes, France
  • 9Department of Gynecology-Obstetrics, Poissy St-Germain Hospital, Poissy, France
  • 10Assistance Publique–Hôpitaux de Paris, Department of Endocrinology, St Antoine Hospital Paris, France
  • 11Department of Obstetrics, Gynecology and Fetal Medicine, University Hospital Center of Tours, Tours, France
  • 12Department of Endocrinology, Caen University Hospital, Caen, France, France
  • 13Department of Endocrinology, Rouen University Hospital–Charles Nicolle, Rouen, France
  • 14Department of Endocrinology, St Joseph Hospital, Marseille, France
  • 15Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France
  • 16Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France
  • 17Assistance Publique–Hôpitaux de Marseille; AMU, Aix-Marseille Université, Department of Gynecology and Obstetrics, Pole Femme Enfant, Marseille, France
  • 18Assistance Publique–Hôpitaux de Paris, Department of Hepato-Enterology-Gastroenteritis, Béclère Hospital, Clamart, France
  • 19Department of Gynecology-Obstetrics, Toulouse University Hospital, Toulouse, France
  • 20Department of Gynecology-Obstetrics, Lille University, EA 4489–Environnement Périnatal et Santé, Lille, France
  • 21Assistance Publique–Hôpitaux de Paris, Department of Gynecology-Obstetrics, Trousseau Hospital, Paris, France
  • 22Department of Internal Medicine, François-Rabelais University, University Hospital Center of Tours, Tours, France
  • 23Department of Gynecology-Obstetrics, Caen University Hospital, Caen, France, France
  • 24Department of Gynecology and Obstetrics, Rouen University Hospital–Charles Nicolle, Rouen, France
  • 25Department of Gynecology-Obstetrics, St Joseph Hospital, Marseille, France
  • 26Department of Endocrinology, Angers University Hospital, Angers, France
  • 27Assistance Publique–Hôpitaux de Paris, Sorbonne Universities, University Pierre and Marie Curie, University Paris 06, Department of Neonatology, Armand Trousseau Hospital, Paris, France
JAMA. 2018;319(17):1773-1780. doi:10.1001/jama.2018.4072
Key Points

Question  Does use of glyburide compared with subcutaneous insulin result in an increase in perinatal complications among women with gestational diabetes?

Findings  In this noninferiority randomized trial that included 914 pregnant women with gestational diabetes, the rate of the composite criterion (including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia) was 27.6% with glyburide and 23.4% with insulin; the upper confidence limit of the difference was 10.5%, which exceeded the prespecified noninferiority margin of 7%.

Meaning  These findings do not support noninferiority of glyburide for prevention of perinatal complications of gestational diabetes.

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

×