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Randomised cross-over trial of vildagliptin and pioglitazone as add-on therapy in patients with type 2 diabetes: predicting Which One is Right Here (WORTH) study protocol
  1. Rui Qian Yeu1,2,
  2. Rebecca Brandon1,2,
  3. Yannan Jiang3,
  4. Dale Griffiths4,
  5. Kate Smallman5,
  6. Allan Moffitt6,
  7. Glenn Doherty7,
  8. Ryan Paul8,
  9. Jennie Harré Hindmarsh9,
  10. Tony R Merriman10,
  11. Kerry Macaskill-Smith11,
  12. Brandon Orr-Walker12,
  13. Rinki Murphy1,2
  1. 1Medicine, The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
  2. 2Auckland Diabetes Centre, Auckland City Hospital, Auckland, New Zealand
  3. 3Department of Statistics, The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
  4. 4Zoom Pharmacy, Auckland, New Zealand
  5. 5Diabetes Foundation Aotearoa, Auckland, New Zealand
  6. 6ProCARE Health Limited, Auckland, New Zealand
  7. 7Tongan Health Society, Auckland, New Zealand
  8. 8University of Waikato, Hamilton, New Zealand
  9. 9Ngati Porou Hauora, Te Puia Springs, Tairawhiti, New Zealand
  10. 10School of Medical Sciences, University of Otago, Dunedin, New Zealand
  11. 11Ventures Limited, Hamilton, New Zealand
  12. 12Endocrinology and Diabetes Service, Counties Manukau District Health Board, Auckland, New Zealand
  1. Correspondence to Dr Rinki Murphy; r.murphy{at}auckland.ac.nz

Abstract

Introduction There is emerging evidence for stratified glucose-lowering responses to certain oral medications for type 2 diabetes (T2D) by individual characteristics. The objective of this study was to test whether glycaemic response to representative treatments of dipeptidyl peptidase-4 inhibitors (vildagliptin) and thiazolidinediones (pioglitazone) varies according to ethnicity, gender, baseline obesity, triglyceride level or genetic variation.

Methods This is a multicentre, two-period, two-treatment, open-label, randomised cross-over trial of vildagliptin and pioglitazone as second-line or third-line therapy in patients with T2D who have suboptimal glycaemic control on metformin and/or sulfonylurea therapy. It is conducted in New Zealand with a target of 300 patients (40% with Māori or Pacific ancestry) eligible if aged ≥18 and ≤80 years, with T2D for more than 1 year, on stable doses of metformin and/or sulfonylurea for at least 3 months, with HbA1c between 59 and 110 mmol/mol inclusive. Participants are assigned to complete 4 months of vildagliptin 50 mg per day or pioglitazone 30 mg per day, followed by 4 months of the other medications in randomly allocated sequences. Participant characteristics, including ethnicity, obesity, lipid profile and candidate genotypes are collected at baseline. Primary outcome variable is on treatment HbA1c. Secondary outcomes include weight change, frequency of side effects and patient preference.

Ethics and dissemination Ethical approval of the trial has been obtained from the New Zealand Health and Disability Ethics Committee (18/STH/242). The trial commenced in February 2019 and recruitment is expected to be completed by March 2020. Results will be reported in articles submitted to peer-reviewed journals, as well as in presentations at national and international meetings.

Trial registration number ACTRN12618001907235.

  • general diabetes
  • diabetes and endocrinology
  • statistics and research methods
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Footnotes

  • Contributors RY wrote the first draft of the manuscript based on the study protocol written by RM, who conceived the study idea, obtained the funding and is the guarantor of the study. YJ is primarily responsible for the statistics analysis plan. TRM is responsible for the genetic analysis plan. DG contributed to the study design as lead pharmacist. Trial implementation, conduct and data acquisition were conducted by RB, AM, GD, RP, JHH, BO-W and KM-S). All authors read and approved the final version of the manuscript.

  • Funding This work was supported by the Health Research Council of New Zealand (grant number 18/681) and a Middlemore Clinical Trials Project grant. Neither the study sponsor (University of Auckland, host institution of the principal investigator) nor the funders have any role in the study design, data collection, management, analysis or interpretation of the data.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

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

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