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

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


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.

Publication types

  • Comparative Study
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glyburide

Associated data

  • ClinicalTrials.gov/NCT01731431