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Randomized Controlled Trial
. 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

Marie-Victoire Sénat  1   2   3 , Helene Affres  4 , Alexandra Letourneau  5 , Magali Coustols-Valat  6 , Marie Cazaubiel  7 , Helene Legardeur  8 , Julie Fort Jacquier  9 , Nathalie Bourcigaux  10 , Emmanuel Simon  11 , Anne Rod  12 , Isabelle Héron  13 , Virginie Castera  14 , Loic Sentilhes  15   16 , Florence Bretelle  17 , Catherine Rolland  18 , Mathieu Morin  19 , Philippe Deruelle  20 , Celine De Carne  21 , François Maillot  22 , Gael Beucher  23 , Eric Verspyck  24 , Raoul Desbriere  25 , Sandrine Laboureau  26 , Delphine Mitanchez  27 , Jean Bouyer  3 ; Groupe de Recherche en Obstétrique et Gynécologie (GROG)
Affiliations
Randomized Controlled Trial

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

Marie-Victoire Sénat et al. JAMA. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sentilhes reports consultancy work and lecturing for Ferring Laboratories. No other disclosures were reported.

Figures

Figure.
Figure.. Participant Flow in the Insulin Daonil Trial
aData on women who were screened for eligibility and reasons why some of them were not randomized were not recorded and are not shown.
See this image and copyright information in PMC

Comment in

References

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