PMID- 33371044 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20240331 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 10 IP - 12 DP - 2020 Dec 21 TI - 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. PG - e042784 LID - 10.1136/bmjopen-2020-042784 [doi] LID - e042784 AB - 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 (HbA(1c)) >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 HbA(1c) 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. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. FAU - Angwin, Catherine AU - Angwin C AUID- ORCID: 0000-0002-0935-5284 AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, Devon, UK. FAU - Jenkinson, Caroline AU - Jenkinson C AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, Devon, UK. FAU - Jones, Angus AU - Jones A AUID- ORCID: 0000-0002-0883-7599 AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, Devon, UK. FAU - Jennison, Christopher AU - Jennison C AD - Department of Mathematical Sciences, University of Bath, Bath, Somerset, UK. FAU - Henley, William AU - Henley W AD - Health Statistics Group, University of Exeter Medical School, University of Exeter, Exeter, UK. FAU - Farmer, Andrew AU - Farmer A AUID- ORCID: 0000-0002-6170-4402 AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. FAU - Holman, Rury R AU - Holman RR AD - Radcliffe Department of Medicine, University of Oxford Medical Sciences Division, Oxford, UK. FAU - Pearson, Ewan AU - Pearson E AD - University of Dundee, Dundee, Dundee, UK. FAU - Shields, Beverley AU - Shields B AUID- ORCID: 0000-0003-3785-327X AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, Devon, UK b.shields@exeter.ac.uk. FAU - Hattersley, Andrew AU - Hattersley A AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, Devon, UK. CN - MASTERMIND consortium LA - eng SI - ClinicalTrials.gov/NCT02653209 GR - 098395/Z/12/Z/WT_/Wellcome Trust/United Kingdom GR - MR/N00633X/1/MRC_/Medical Research Council/United Kingdom GR - 102820/Z/13/Z/WT_/Wellcome Trust/United Kingdom GR - RE/18/6/34217/BHF_/British Heart Foundation/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201221 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - EC 3.4.14.5 (DPP4 protein, human) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) SB - IM MH - Cross-Over Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Dipeptidyl Peptidase 4/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Double-Blind Method MH - Drug Therapy, Combination MH - England MH - Glycated Hemoglobin/analysis MH - Glycemic Control MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Metformin/therapeutic use MH - *Pharmaceutical Preparations MH - Randomized Controlled Trials as Topic MH - Scotland MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - State Medicine MH - *Thiazolidinediones/therapeutic use MH - Treatment Outcome MH - Wales PMC - PMC7754630 OTO - NOTNLM OT - clinical trials OT - diabetes & endocrinology OT - therapeutics COIS- Competing interests: EP has received Honoraria from Lilly. NS has consulted for Amgen, Astrazeneca, Boehringer Ingelheim, Eli-Lilly, Napp, NovoNordisk, Sanofi and Pfizer and received grant funding from Boehringer Ingelheim. RRH reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Bayer, Intarcia, Merck Sharp & Dohme, Novartis and Novo Nordisk outside the submitted work. CJ has consulted for AstraZeneca, Boehringer Ingelheim, NovoNordisk and Sanofi. WH has received grant funding from IQVIA and travel funds from Eisai. EDAT- 2020/12/30 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/12/21 CRDT- 2020/12/29 01:02 PHST- 2020/12/29 01:02 [entrez] PHST- 2020/12/30 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/12/21 00:00 [pmc-release] AID - bmjopen-2020-042784 [pii] AID - 10.1136/bmjopen-2020-042784 [doi] PST - epublish SO - BMJ Open. 2020 Dec 21;10(12):e042784. doi: 10.1136/bmjopen-2020-042784.