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JAMA. 2018 May 1;319(17):1773-1780. doi: 10.1001/jama.2018.4072.

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

Author information

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

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.

PMID:
29715355
DOI:
10.1001/jama.2018.4072
[Indexed for MEDLINE]

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