BMJ Open (Aug 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
- Floris Groenendaal,
- Arie Franx,
- Rebecca C Painter,
- Ben Willem Mol,
- Bas B Van rijn,
- 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 Klooker,
- Rosemarie 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,
- Inge M Evers,
- Harold W de Valk,
- J Hans deVries
Affiliations
- Floris Groenendaal
- 1 Neonatology, Wilhelmina Children`s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
- Arie Franx
- Netherlands Federation of University Medical Centers, Utrecht, Netherlands
- Rebecca C Painter
- Department of Obstetrics and Gynecology, University of Amsterdam, Amsterdam, The Netherlands
- Ben Willem Mol
- 2 Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
- Bas B Van rijn
- 1 Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Leon de Wit
- 1 Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Doortje Rademaker
- 2 Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Daphne N Voormolen
- 1 Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Bettina M C Akerboom
- 3 Department of Obstetrics and Gynaecology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
- Rosalie M Kiewiet-Kemper
- 4 Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands
- Maarten R Soeters
- 5 Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Marion A L Verwij-Didden
- 6 Department of Obstetrics and Gynaecology, Bernhoven Hospital, Uden, The Netherlands
- Fahima Assouiki
- 7 Department of Internal Medicine, Bernhoven Hospital, Uden, The Netherlands
- Daniela H Schippers
- 8 Department of Obstetrics and Gynaecology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
- Mechteld A R Vermeulen
- 9 Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
- Simone M I Kuppens
- 10 Department of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, The Netherlands
- Mirjam M Oosterwerff
- 11 Department of Internal Medicine, Catharina Hospital, Eindhoven, The Netherlands
- Joost J Zwart
- 12 Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands
- Mattheus J M Diekman
- 13 Department of Internal Medicine, Deventer Hospital, Deventer, The Netherlands
- Tatjana E Vogelvang
- 14 Department of Obstetrics and Gynaecology, Diakonessenhuis Utrecht, Utrecht, The Netherlands
- P Rob J Gallas
- 15 Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands
- Sander Galjaard
- 16 Department of Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Willy Visser
- 16 Department of Obstetrics and Prenatal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Nicole Horree
- 17 Department of Obstetrics and Gynaecology, Flevoziekenhuis, Almere, The Netherlands
- Tamira K Klooker
- 18 Department of Internal Medicine, Flevoziekenhuis, Almere, The Netherlands
- Rosemarie Laan
- 19 Department of Obstetrics and Gynaecology, Gelderse Vallei Hospital, Ede, The Netherlands
- Rik Heijligenberg
- 20 Department of Internal Medicine, Gelderse Vallei Hospital, Ede, The Netherlands
- Anjoke J M Huisjes
- 21 Department of Obstetrics and Gynaecology, Gelre Hospitals, Apeldoorn, The Netherlands
- Thomas van Bemmel
- 22 Department of Internal Medicine, Gelre Hospitals, Apeldoorn, The Netherlands
- Claudia A van Meir
- 23 Department of Obstetrics and Gynaecology, Groene Hart Hospital, Gouda, The Netherlands
- Annewieke W van den Beld
- 24 Department of Internal Medicine, Groene Hart Hospital, Gouda, The Netherlands
- Wietske Hermes
- 25 Department of Obstetrics and Gynaecology, Haaglanden Medical Center, The Hague, The Netherlands
- Solrun Vidarsdottir
- 26 Department of Internal Medicine, Haaglanden Medical Center, The Hague, The Netherlands
- Anneke G Veldhuis-Vlug
- 27 Department of Internal Medicine, Medical Center Jan van Goyen, Amsterdam, The Netherlands
- Remke C Dullemond
- 28 Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands
- Henrique J Jansen
- 29 Department of Internal Medicine, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands
- Marieke Sueters
- Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
- Eelco J P de Koning
- 31 Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Judith O E H van Laar
- Department of Obstetrics & Gynaecology, Máxima Medical Center, Veldhoven, The Netherlands
- Pleun Wouters-van Poppel
- 33 Department of Internal Medicine, Máxima Medical Center, Veldhoven, The Netherlands
- Marina E Sanson-van Praag
- 34 Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands
- Eline S van den Akker
- 35 Department of Obstetrics and Gynaecology, OLVG, Amsterdam, The Netherlands
- Catherine B Brouwer
- 36 Department of Internal Medicine, OLVG, Amsterdam, The Netherlands
- Brenda B Hermsen
- 35 Department of Obstetrics and Gynaecology, OLVG, Amsterdam, The Netherlands
- Bert Jan Potter van Loon
- 36 Department of Internal Medicine, OLVG, Amsterdam, The Netherlands
- Olivier W H van der Heijden
- 37 Department of Obstetrics and Gynaecology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
- Bastiaan E de Galan
- 38 Department of Internal Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
- Marsha van Leeuwen
- 39 Department of Obstetrics and Gynaecology, Reinier de Graaf Hospital, Delft, The Netherlands
- Johanna A M Wijbenga
- 40 Department of Internal Medicine, Reinier de Graaf Hospital, Delft, The Netherlands
- Karin de Boer
- 41 Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands
- Arianne C van Bon
- Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands
- Flip W van der Made
- 43 Department of Obstetrics and Gynaecology, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands
- Silvia A Eskes
- 44 Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands
- Mirjam Zandstra
- 45 Department of Obstetrics and Gynaecology, Spaarne Gasthuis, Haarlem, The Netherlands
- William H van Houtum
- 46 Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
- Babette A M Braams-Lisman
- 47 Department of Obstetrics and Gynaecology, Tergooi, Blaricum, The Netherlands
- Catharina R G M Daemen-Gubbels
- 48 Department of Internal Medicine, Tergooi, Blaricum, The Netherlands
- Maurice G A J Wouters
- 49 Department of Obstetrics and Gynaecology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
- Richard G IJzerman
- 50 Department of Internal Medicine, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
- Nico A Mensing van Charante
- 51 Department of Obstetrics and Gynaecology, Dijklander Hospital, Hoorn, The Netherlands
- Rolf Zwertbroek
- 52 Department of Internal Medicine, Dijklander Hospital, Hoorn, The Netherlands
- Inge M Evers
- 54 Department of Obstetrics and Gynaecology, Meander Medical Center, Amersfoort, The Netherlands
- Harold W de Valk
- Vascular Medicine and Endocrinology, UMC Utrecht, Utrecht, The Netherlands
- J Hans deVries
- Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- DOI
- https://doi.org/10.1136/bmjopen-2019-029808
- Journal volume & issue
-
Vol. 9,
no. 8
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.
