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

Marie-Victoire Senat (1, 2, 3) , Helene Affres , Alexandra Letourneau , Magali Coustols-Valat , Marie Cazaubiel , Helene Legardeur , Julie Fort Jacquier , Nathalie Bourcigaux , Emmanuel Simon , Anne Rod , Isabelle Heron , Virginie Castera , Loic Sentilhes (4) , Florence Bretelle (5, 6) , Catherine Rolland (7) , Mathieu Morin (8) , Philippe Deruelle (9) , Celine de Carne (10) , Francois Maillot (11) , Gael Beucher (12) , Eric Verspyck (13) , Raoul Desbriere , Sandrine Laboureau , Delphine Mitanchez (14, 10) , Jean Bouyer (1) , Grp Rec Obstetrique Gynecologie

1 CESP - Centre de recherche en épidémiologie et santé des populations
2 Service de Gynécologie Obstétrique [AP-HP Hôpital Bicêtre]
3 UP11 UFR Médecine - Université Paris-Sud - Paris 11 - Faculté de médecine
4 Service d'Obstétrique et Gynécologique [Angers]
5 Gynépole
6 MEPHI - Microbes évolution phylogénie et infections
7 UGA UFRP - Université Grenoble Alpes - UFR Pharmacie
8 Service Gynécologie [CHU Toulouse]
9 Service de Gynécologie - Obstétrique [Lille]
10 CHU Trousseau [APHP]
11 Hôpital Bretonneau
12 Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen]
13 Service de Gynécologie et Obstétrique [CHU Rouen]
14 UPMC - Université Pierre et Marie Curie - Paris 6

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 outcomewas 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, -infinity 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.

Domaines: Maladies infectieuses

Marie-Victoire Senat, Helene Affres, Alexandra Letourneau, Magali Coustols-Valat, Marie Cazaubiel, et al.. Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes A Randomized Clinical Trial. Journal of the American Medical Association, 2018, 319 (17), pp.1773-1780. ⟨10.1001/jama.2018.4072⟩. ⟨hal-01791582⟩