SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial
Authors: de Wit Leon , Rademaker Doortje , Voormolen Daphne N , Akerboom Bettina M C , Kiewiet-Kemper Rosalie M , Soeters Maarten R , Verwij-Didden Marion A L , Assouiki Fahima , Schippers Daniela H , Vermeulen Mechteld A R , Kuppens Simone M I , Oosterwerff Mirjam M , Zwart Joost J , Diekman Mattheus J M , Vogelvang Tatjana E , Gallas P Rob J , Galjaard Sander , Visser Willy , Horree Nicole , Klooker Tamira K , Laan Rosemarie , Heijligenberg Rik , Huisjes Anjoke J M , van Bemmel Thomas , van Meir Claudia A , van den Beld Annewieke W , Hermes Wietske , Vidarsdottir Solrun , Veldhuis-Vlug Anneke G , Dullemond Remke C , Jansen Henrique J , Sueters Marieke , de Koning Eelco J P , van Laar Judith O E H , Wouters-van Poppel Pleun , Sanson-van Praag Marina E , van den Akker Eline S , Brouwer Catherine B , Hermsen Brenda B , Potter van Loon Bert Jan , van der Heijden Olivier W H , de Galan Bastiaan E , van Leeuwen Marsha , Wijbenga Johanna A M , de Boer Karin , van Bon Arianne C , van der Made Flip W , Eskes Silvia A , Zandstra Mirjam , van Houtum William H , Braams-Lisman Babette A M , Daemen-Gubbels Catharina R G M , Wouters Maurice G A J , IJzerman Richard G , Mensing van Charante Nico A , Zwertbroek Rolf , Bosmans Judith E , Evers Inge M , Mol Ben Willem , de Valk Harold W , Groenendaal Floris , Naaktgeboren Christiana A , Painter Rebecca C , deVries J Hans , Franx Arie , van Rijn Bas B 
Published: August 2019

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.

Trial registration number

NTR6134; Pre-results.