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Oral medication strategy versus insulin for diabetes in pregnancy

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To assess the clinical efficacy, safety, cost-effectiveness and patient experience of oral antidiabetic treatment as first-choice agents to treat GDM compared to the conventional insulin treatment strategy.

Open label, multicenter, non-inferiority, randomized controlled trial(RCT).

Study population:

Pregnant women diagnosed with GDM, failing to reach glycemic control with dietary adjustments, requiring additional treatment with antidiabetic medication, between the gestational age of 16 to 34 weeks.

Inclusion criteria:

  • Women >    18 years old with a singleton pregnance
  • Pregnancy is complicated by gestational diabetes as per national guidelines
  • Indication for medical treatment
  • Gestational age of 16 to 34 weeks
  • Able to give informed consent
  • Able to understand Dutch or English
Exclusion criteria:
  • Suffering from severe medical or psychological comorbidities
  • Suffering from severe liver- or kidney failure
  • Pregnancy with a fetus affected by major congenital birth defects and/or chromosomal abnormalities
  • Pre-existing type I or II diabetes
Eligible women will be randomized for either treatment with oral antidiabetic medication consisting of metformin and if needed additional glibenclamide or insulin.

Outcome measures:
Primary outcome: large-for-gestational-age (LGA) defined as a birth weight >90th percentile.
Secondary outcomes: maternal diabetic endpoints (hypoglycemia, time to reach glycemic control, HbA1c), maternal weight gain, treatment failure, pregnancy complications (pregnancy related hypertensive disorders, preterm delivery), birth injury, Caesarean section,neonatal complications (hypoglycemia, hyperbilirubinemia, NICUadmission), umbilical cord markers for hyperinsulinemia, patient satisfaction and health-related quality of life (EQ5-5D-5L and DTSQ questionnaires), costs from a societal perspective.

Power/data analysis:

This study will be a two-armed non-inferiority trial(metformin/glibenclamide versus insulin). The anticipated incidence of the primary outcome measure (LGA) is 20% in both groups. We have set the non-inferiority limit at 8%, which is equivalent to excluding a relative risk greater than 1.4. With a one-sided significance level() of 0.025 and a power of 0.8, the sample size was calculated at393 patients in each arm. Accounting for a loss to follow-up of 3%,810 patients are needed.

Economic evaluation:
Acost-effectiveness analysis will be performed, taking into accountthe costs of the different treatment strategies, health-care consumption and productivity losses from inclusion in the study up to 6 weeks postpartum.

Time schedule:
36 months: 6 months preparation, 24 months inclusion, 6 months analysis and report.

Project leaders:

Dr. B.B. van Rijn, gynaecologist, UMC Utrecht
Prof. dr. A. Franx, gynaecologist, UMC Utrecht
Prof. dr. J.H. de Vries, internal medicine endocrinologist, AMC Amsterdam

Health technology Assessment:

Dr. J.E. Bosmans, assistant professor, Department of Health & Science, VU Amsterdam


Dr. Christiana Naaktgeboren, assistant professor, UMC Utrecht, c.naaktgeboren@umcutrecht.nl


Contact (researcher):
Drs. Leon de Wit, UMC Utrecht, l.dewit-3@umcutrecht.nl