SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Leon De Wit, Doortje Rademaker, Daphne N. Voormolen, Bettina M.C. Akerboom, Rosalie M. Kiewiet-Kemper, Maarten R. Soeters, Marion A.L. Verwij-Didden, Fahima Assouiki, Daniela H. Schippers, Mechteld A.R. Vermeulen, Simone M.I. Kuppens, Mirjam M. Oosterwerff, Joost J. Zwart, Mattheus J.M. Diekman, Tatjana E. Vogelvang, P. Rob J. Gallas, Sander Galjaard, Willy Visser, Nicole Horree, Tamira K. KlookerRosemarie Laan, Rik Heijligenberg, Anjoke J.M. Huisjes, Thomas Van Bemmel, Claudia A. Van Meir, Annewieke W. Van Den Beld, Wietske Hermes, Solrun Vidarsdottir, Anneke G. Veldhuis-Vlug, Remke C. Dullemond, Henrique J. Jansen, Marieke Sueters, Eelco J.P. De Koning, Judith O.E.H. Van Laar, Pleun Wouters-Van Poppel, Marina E. Sanson-Van Praag, Eline S. Van Den Akker, Catherine B. Brouwer, Brenda B. Hermsen, Bert Jan Potter Van Loon, Olivier W.H. Van Der Heijden, Bastiaan E. De Galan, Marsha Van Leeuwen, Johanna A.M. Wijbenga, Karin De Boer, Arianne C. Van Bon, Flip W. Van Der Made, Silvia A. Eskes, Mirjam Zandstra, William H. Van Houtum, Babette A.M. Braams-Lisman, Catharina R.G.M. Daemen-Gubbels, Maurice G.A.J. Wouters, Richard G. Ijzerman, Nico A. Mensing Van Charante, Rolf Zwertbroek, Judith E. Bosmans, Inge M. Evers, Ben Willem Mol, Harold W. De Valk, Floris Groenendaal, Christiana A. Naaktgeboren, Rebecca C. Painter, J. Hans Devries, Arie Franx, Bas B. Van Rijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere029808
JournalBMJ Open
Volume9
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019

Cite this

De Wit, L., Rademaker, D., Voormolen, D. N., Akerboom, B. M. C., Kiewiet-Kemper, R. M., Soeters, M. R., ... Van Rijn, B. B. (2019). SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial. BMJ Open, 9(8), [e029808]. https://doi.org/10.1136/bmjopen-2019-029808