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Comparative Study
. 2019 Aug 18;9(8):e029808.
doi: 10.1136/bmjopen-2019-029808.

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  1 , Doortje Rademaker  2 , Daphne N Voormolen  1 , Bettina M C Akerboom  3 , Rosalie M Kiewiet-Kemper  4 , Maarten R Soeters  5 , Marion A L Verwij-Didden  6 , Fahima Assouiki  7 , Daniela H Schippers  8 , Mechteld A R Vermeulen  9 , Simone M I Kuppens  10 , Mirjam M Oosterwerff  11 , Joost J Zwart  12 , Mattheus J M Diekman  13 , Tatjana E Vogelvang  14 , P Rob J Gallas  15 , Sander Galjaard  16 , Willy Visser  16 , Nicole Horree  17 , Tamira K Klooker  18 , Rosemarie Laan  19 , Rik Heijligenberg  20 , Anjoke J M Huisjes  21 , Thomas van Bemmel  22 , Claudia A van Meir  23 , Annewieke W van den Beld  24 , Wietske Hermes  25 , Solrun Vidarsdottir  26 , Anneke G Veldhuis-Vlug  27 , Remke C Dullemond  28 , Henrique J Jansen  29 , Marieke Sueters  30 , Eelco J P de Koning  31 , Judith O E H van Laar  32 , Pleun Wouters-van Poppel  33 , Marina E Sanson-van Praag  34 , Eline S van den Akker  35 , Catherine B Brouwer  36 , Brenda B Hermsen  35 , Bert Jan Potter van Loon  36 , Olivier W H van der Heijden  37 , Bastiaan E de Galan  38 , Marsha van Leeuwen  39 , Johanna A M Wijbenga  40 , Karin de Boer  41 , Arianne C van Bon  42 , Flip W van der Made  43 , Silvia A Eskes  44 , Mirjam Zandstra  45 , William H van Houtum  46 , Babette A M Braams-Lisman  47 , Catharina R G M Daemen-Gubbels  48 , Maurice G A J Wouters  49 , Richard G IJzerman  50 , Nico A Mensing van Charante  51 , Rolf Zwertbroek  52 , Judith E Bosmans  53 , Inge M Evers  54 , Ben Willem Mol  55 , Harold W de Valk  56 , Floris Groenendaal  57 , Christiana A Naaktgeboren  58 , Rebecca C Painter  2 , J Hans deVries  59 , Arie Franx  1 , Bas B van Rijn  1   16
Affiliations
Comparative Study

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 et al. BMJ Open. .

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.

Trial registration number: NTR6134; Pre-results.

Keywords: clinical trials; diabetes in pregnancy; maternal medicine.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Flowchart of comparator (oral glucose lowering drugs) versus control (insulin). GDM, gestational diabetes mellitus.
See this image and copyright information in PMC

References

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