Funder: Medical Research Council (MRC) MR/N00633X/1
A research study to help improve treatment of type 2 diabetes, by learning how individuals respond to different blood sugar-lowering drugs
Study lay summary
TriMaster – a research study to help improve treatment of type 2 diabetes, by learning how individuals respond to different blood sugar-lowering drugs.
Type 2 Diabetes is a common health condition where an individual has difficulty controlling their blood sugar (glucose). It is common for additional treatments to be added over time to maintain, or lower, blood sugar levels. The current NICE guidelines list a number of drugs without giving clear guidance on which patients should have which treatments.
We know that the response to drugs is variable and their effect may be different between and within individuals. However, very little is known about why this response is different or whether it would be possible to predict if a drug is likely to work for someone. If we could predict which treatment is likely to work for an individual, we could choose the most effective treatment, avoiding ineffective drugs and unnecessary side effects.
This study is looking at three standard diabetes treatments which can be added when one or two existing drugs stop maintaining good blood sugar levels. 600 patients with type 2 diabetes who currently take one or two treatments but need an additional therapy will be recruited at approximately 20 sites across the UK.
Each patient will take each study drug in addition to their existing treatment for four months at a time. At the end of each treatment the patient’s glucose control will be measured and information about their experience of the drug will be collected. We will compare how different patients respond and which treatment they prefer.
The aim of this trial is to identify subgroups of patients with type 2 diabetes that respond well or poorly to particular drugs based on particular clinical characteristics such as their weight or kidney function, to enable better targeting of treatment for a particular individual.
Aim: To undertake a large crossover study of three classes of oral third-line glucose-lowering therapies: i) sitagliptin, a DPP4 inhibitor ii) pioglitazone, a thiazolidinedione and iii) canagliflozin, a SGLT2 inhibitor.
Trial Type, Trial Period, Recruitment Target
Phase 4 randomised double-blind crossover trial
An interventional randomised controlled trial of standard diabetes treatment.
Trial period: April 2016 – January 2020.
Recruitment target: 600
Primary & Secondary Outcomes
The primary objective of the trial is to test the differing response to diabetes therapies, specifically:
Do obese patients (BMI >30kgm-2), compared to non-obese patients, achieve a lower HbA1c when assigned pioglitazone rather than sitagliptin?
Do patients with an eGFR <90 mls/min/1.73m2 achieve a lower HbA1c, compared to patients with an eGFR >90 mls/min/1.73m2, when assigned a sitagliptin rather than canagliflozin
Primary outcome measure:
On-treatment glycated haemoglobin (HbA1c) measurement after 16 weeks on study treatment. Measurement taken in fasting plasma sample.
Secondary outcome measure:
Patient treatment preference of study drug collected at study conclusion
Prevalence of side effects
On treatment HbA1c by gender
Clinical diagnosis of Type 2 diabetes
Age ≥30 and ≤80
Currently treated with either metformin alone or two classes of oral glucose-lowering therapy (given either as separate or combined medications), that do not include a DPP4-inhibitor, a SGLT2-inhibitor or a thiazolidinedione.
Diabetes duration ≥ 12 months
No change in diabetes treatment (new treatments or dose change) within previous 3 months
HbA1c > 58mmol/mol (7.5%) and ≤110mmol/mol (12.2%)