Eligible women will be randomized for either treatment with oral antidiabetic medication consisting of metformin and if needed additional glibenclamide or insulin.
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.
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(á) 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.
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.
36 months: 6 months preparation, 24 months inclusion, 6 months analysis and report.
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, firstname.lastname@example.org
Drs. Leon de Wit, UMC Utrecht, email@example.com