TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol

Angwin, C. et al. (2020) TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol. BMJ Open, 10(12), e042784. (doi: 10.1136/bmjopen-2020-042784) (PMID:33371044) (PMCID:PMC7754630)

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Abstract

Introduction: Pharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents. Methods and analysis: TriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase‐4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12–18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects. Ethical approval: This study was approved by National Health Service Health Research Authority Research Ethics Committee South Central—Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants. Trial registration numbers: 12039221; 2015-002790-38 and NCT02653209.

Item Type:Articles
Additional Information:This work is part of the MASTERMIND (MRC APBI Stratification and Extreme Response Mechanism IN Diabetes) consortium and is supported by the UK Medical Research Council study grant number MR/N00633X/1. The TriMaster trial is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. EP holds a Wellcome Trust New Investigator Award (102820/Z/13/Z). AJ is supported by an NIHR Clinician Scientist award (CS-2015- 15-018). NS is supported by a BHF Centre of Excellence Award (RE/18/6/34217). RRH is an Emeritus National Institute for Health Research Senior Investigator. AH is a Wellcome Senior Investigator (098395/Z/12/Z) and a Senior Investigator at the NIHR. AH, AJ, BS and CA are supported by the NIHR Exeter Clinical Research Facility. AF is an NIHR Senior Investigator and receives support from NIHR Oxford Biomedical Research Centre.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sattar, Professor Naveed
Authors: Angwin, C., Jenkinson, C., Jones, A., Jennison, C., Henley, W., Farmer, A., Sattar, N., Holman, R. R., Pearson, E., Shields, B., and Hattersley, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:BMJ Open
Publisher:BMJ Publishing Group
ISSN:2044-6055
ISSN (Online):2044-6055
Published Online:21 December 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in BMJ Open 10(12): e042784
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science