SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial
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 Valk, Harold W.; Groenendaal, Floris; Naaktgeboren, Christiana A.; Painter, Rebecca C.; Franx, Arie; Van Rijn, Bas B.
(2019) BMJ Open, volume 9, issue 8
(Article)
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
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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.
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Keywords: clinical trials, diabetes in pregnancy, maternal medicine, Diabetes, Gestational/blood, Administration, Oral, Humans, Gestational Age, Pregnancy, Metformin/therapeutic use, Multicenter Studies as Topic, Blood Glucose/drug effects, Cost-Benefit Analysis, Glyburide/therapeutic use, Female, Hypoglycemic Agents/therapeutic use, Drug Therapy, Combination, Equivalence Trials as Topic, Insulin/therapeutic use, Pregnancy Outcome, General Medicine, Research Support, Non-U.S. Gov't, Journal Article, Comparative Study
ISSN: 2044-6055
Publisher: BMJ Publishing Group
Note: Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2019 Author(s).
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