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  • Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)

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Diabetes and endocrinology
Protocol
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)
  1. Kristine Færch1,
  2. Hanan Amadid1,
  3. Lea Bruhn Nielsen1,
  4. Mathias Ried-Larsen2,3,
  5. Kristian Karstoft2,
  6. Frederik Persson1,
  7. Marit Eika Jørgensen1,4
  1. 1 Clinical Epidemiology, Steno Diabetes Center, Gentofte, Denmark
  2. 2 Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  3. 3 Danish Diabetes Academy, Odense, Denmark
  4. 4 National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark
  1. Correspondence to Dr Kristine Færch; kristine.faerch{at}regionh.dk

Abstract

Introduction The primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c (HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.

Methods and analysis The Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.

Ethics and dissemination The study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed.

Trial registration NCT02695810

  • PREVENTIVE MEDICINE
  • DIABETES & ENDOCRINOLOGY
  • PUBLIC HEALTH

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2016-013802

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    Footnotes

    • Contributors KF, FP and MEJ conceived the idea and designed the study. KF sponsors the trial and owns the data. MEJ is principal investigator. HA and LBN are coinvestigators. MR-L and KK have contributed to the design of the exercise intervention. KF has drafted the manuscript. All authors have read and approved the final version of the manuscript.

    • Funding This work was initiated by Kristine Færch, MSc PhD, Steno Diabetes Center A/S. The study is funded by an unrestricted grant from the Novo Nordisk Foundation as an investigator-initiated study. The research project is conducted with support from AstraZeneca AB, Ascensia Diabetes Care, the Danish Innovation Foundation, and the University of Copenhagen. Mathias Ried-Larsen is funded by a postdoc grant from the Danish Diabetes Academy (supported by the Novo Nordic Foundation).

    • Disclaimer The funders have no role in study design, data collection and analysis, decision to publish, or preparation of manuscripts.

    • Competing interests KF, HA, LBN, FP and MEJ are employed by Steno Diabetes Center, a research hospital working in the Danish National Health Service. Until 31 December 2016 Steno Diabetes Center has been owned by Novo Nordisk A/S and has received part of its core funding from unrestricted grants from the Novo Nordisk Foundation and Novo Nordisk A/S. KF and MEJ own shares in Novo Nordisk A/S. KF, FP and MEJ have received research support from AstraZeneca. FP reports having received research grant from Novartis and lecture fees from MSD, AstraZeneca, Novo Nordisk, Novartis, Eli Lilly and Boehringer Ingelheim, and have served as a consultant for AstraZeneca and MSD.

    • Ethics approval Ethics Committee of the Capital Region (H-15011398) and the Danish Medicines Agency (EudraCT number: 2015-001552-30).

    • Provenance and peer review Not commissioned; externally peer reviewed.