TriMaster v1
Research type
Research Study
Full title
TriMaster: Randomised Double-Blind Crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as third line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on dual therapy with metformin and a sulphonylurea
IRAS ID
183044
Contact name
Chris Gardner
Contact email
Sponsor organisation
Royal Devon & Exeter NHS Foundation Trust
Eudract number
2015-002790-38
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 11 months, 31 days
Research summary
Research Summary
The TriMaster trial is part of the larger MASTERMIND project which aims to help identify the most suitable treatment for patients with type 2 diabetes.
It is known that patients with type 2 diabetes vary greatly in how well they respond to different diabetes drugs and whether they develop side effects to particular medications. In this study the research team aims to identify subgroups of patients that respond well or poorly to third-line therapies based on particular clinical characteristics such as their BMI and renal function.
The current choice for non-injectable third-line therapy is between a DPP4 inhibitor, an SGLT2 inhibitor and a thiazolidinedione (TZD). However the decision of which treatment to choose lacks guidance on which patients will respond well or poorly to a particular therapy.
This study is a randomised double-blind crossover trial in patients with type 2 diabetes who have poor glucose control on two classes of drugs. Patients who meet the current NICE guidelines for the addition of a third-line drug will be invited to take the 3 different available therapies for 4.5 months each in random order. As these drugs work in different ways the research team will be able to test whether the different clinical characteristics affect whether they respond well to the drugs, and/or make them more likely to experience side effects.
Eligible patients will be recruited and undertake a baseline research visit before being randomised. Participants will then receive 4.5 months of each blinded therapy in random order, with a fasting blood test taken at the end of each period. In addition to measuring blood glucose and weight, the research team will collect data on participant preference, side effects experienced and preparedness to continue taking the drug long-term at the end of each study period. Participants will rank the 3 therapies on study completion.
Summary of Results
Background We wanted to understand why some diabetes medicines work better for some people so that we can help to choose the most effective medicine in the future. In type 2 diabetes, it is common for additional treatments to be added over time to maintain, or lower, blood sugar levels. We know that the response to these medications can be variable and their effect may be different between people. However, very little is known about why this response is different or whether it would be possible to predict if a medicine is likely to work for someone. If we could predict which medicine is likely to work for a person, we could choose the most effective treatment, avoiding ineffective medicines and unnecessary side effects. This study looked at three standard diabetes treatments which can be added when one or two existing medicines stop maintaining good blood sugar levels. We compared how patients with different blood sugar levels, weight and kidney function respond, and which treatment each patient preferred.
What did we do?
This study was led by researchers at the University of Exeter with diabetes research teams at 24 centres across the UK. Adults with Type 2 Diabetes who took one or two oral diabetes medications but whose blood sugar levels meant they needed an additional medication were invited to take part. Participants took three standard diabetes drugs alongside their usual medications: pioglitazone, sitagliptin and canagliflozin. The study was a crossover design, meaning each participant took all three drugs in random order, one drug at a time for 16 weeks. At the start of the study, and between each drug participants provided blood samples and answered questions about their experience of the drug. At the end of the study, participants were given the results of their blood sugar levels on each drug and were asked their preference.Funding: This trial was funded by the UK Medical Research Council study and the central team were supported by the National Institute for Health Research Exeter Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the MRC, the NIHR or the Department of Health.
Key Findings:
• When comparing everyone’s results, the three drugs worked equally well at lowering blood sugar. However, we found that using a person’s BMI or a simple blood test that measures their kidney function, can show which drug is likely to be better. This could mean in the future we can tailor treatment to the person instead of recommending the same drug for everyone.
• Heavier people had lower blood sugar with pioglitazone, whereas slimmer people responded better to sitagliptin.
• If a blood test showed that people had very good kidney function, they had lower blood sugar on canagliflozin. If a blood test showed their kidneys weren’t working quite so well, they did better with sitagliptin.
• Most people were able to tolerate the drugs and took them for at least 12 weeks. In the study, if someone had severe side effects and needed to stop a drug they could change to the next one. Pioglitazone was the best tolerated overall, with only 6% of people needing to stop the drug before 12 weeks. 9% of people stopped sitagliptin before 12 weeks, and 9% of people stopped canagliflozin.
• Different people preferred different drugs. When people ranked the drugs, 39% preferred canagliflozin, 35% of people preferred sitagliptin and 26% preferred pioglitazone overall.
• The drug people preferred was usually the one they had the lowest blood sugar on and the fewest side effects.
• The study has shown that the right drug is not the same for everyone and that it is possible to predict how a drug is likely to work using a person’s BMI or kidney function .
This research means we can really start to think about giving patients more tailored advice when deciding which treatment to give to lower their blood sugar.REC name
South Central - Oxford A Research Ethics Committee
REC reference
16/SC/0147
Date of REC Opinion
13 Apr 2016
REC opinion
Favourable Opinion