Samenvatting
Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.
| Originele taal-2 | Engels |
|---|---|
| Artikelnummer | e029808 |
| Aantal pagina's | 9 |
| Tijdschrift | BMJ open |
| Volume | 9 |
| Nummer van het tijdschrift | 8 |
| DOI's | |
| Status | Gepubliceerd - 1 aug. 2019 |
Financiering
This trial has been approved by the Medical Research Ethics Committee (MREC) of the UMC Utrecht. Trial reference number: 16–523/G-M-X. The MREC of the UMC Utrecht is accredited by the Central Committee on Research Involving Human Subjects (CCMO) since November 1999. For all participating hospitals and study sites, approval by the boards of management will be obtained. The CCMO has issued a ‘No grounds for non-acceptance’ for the SUGAR-DIP trial. Research with a medicinal product must undergo an extra, marginal review alongside the review by the reviewing party (MREC). The competent authority (CCMO) checks if there are ‘motivated objections’ against the study. For this the European adverse reactions database (EudraVig-ilance) is checked for any previously reported suspected adverse reactions to the medicinal product, which could lead to unacceptable risks to the participating research subject. Furthermore, the CCMO is responsible as the competent authority for entering data into the European EudraCT database. EudraCT number for this trial: 2016-001401-16. Funding The SUGAR-DIP trial and this work is investigator-driven and was supported by ZonMw (The Netherlands Organisation for Health Research and Development, the Hague), grant 80-83600-98-40001. Competing interests JHD sits on advisory boards for Novo Nordisk A/S. BWM is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). BWM reports consultancy for ObsEva, Merck KGaA and Guerbet.
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