NCT02653209: TriMaster

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

Completed Phase 4 Last updated 30 March 2021

What this trial tests

Phase 4 trial testing Sitagliptin - DPP4i in Type 2 Diabetes in 525 participants. Completed in 1 January 2021.

Timeline

1 November 2016

Primary endpoint
1 January 2021

1 January 2021

Quick facts

Lead sponsor	Royal Devon and Exeter NHS Foundation Trust
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	525
Start date	1 November 2016
Primary completion	1 January 2021
Estimated completion	1 January 2021
Sites	1 location across United Kingdom

Drugs / interventions tested

• Sitagliptin - DPP4i — full drug profile →
• Canagliflozin - SGLT2i — full drug profile →
• Pioglitazone - TZD — full drug profile →

Conditions studied

• Type 2 Diabetes — all drugs for Type 2 Diabetes →

Sponsor

Royal Devon and Exeter NHS Foundation Trust

Who can join

Adults 30 to 80, any sex, with Type 2 Diabetes. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• On treatment HbA1c in obese patients (BMI >30kgm-2), compared to non-obese patients
  Time frame: 16 weeks
  Outcome measure will test hypothesis that patients with insulin resistance, characterised clinically by a raised BMI (\>30 kg/m2), compared to non-obese patients, will: 1. Respond well to pioglitazone, a thiazolidinedione that works as an insulin sensitiser. 2. Respond less well to sitagliptin, a DPP4i, which works through stimulating endogenous insulin secretion post-prandially.
• On treatment HbA1c in patients with an eGFR <90 mls/min/1.73m2 compared to patients with an eGFR >90 mls/min/1.73m2.
  Time frame: 16 weeks
  Outcome measure will test hypothesis that patients with modestly reduced estimated glomerular filtration rate (eGFR 60-90 mls/min/1.73m2), compared to those with eGFR \>90 mls/min/1.73m2, will: 1. Respond poorly to canagliflozin, a SGLT2 inhibitor, which works through inhibiting the active reabsorption of glucose in the proximal tubule, as the reduced eGFR will reduce the glucose-lowering efficac

Sponsor's own description

The aim of this project 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.

This study will test 2 hypotheses of drug response supported by routine clinical and trial data. 600 patients with type 2 diabetes who have suboptimal glycaemic control on dual oral therapy will be recruited to a randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione. 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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Precision Medicine in Type 2 Diabetes: Using Individualized Prediction Models to Optimize Selection of Treatment.
   Dennis JM. · · 2020 · cited 66× · PMID 32843566 · DOI 10.2337/dbi20-0002
2. Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study.
   Shields BM, Dennis JM, Angwin CD, Warren F, et al · · 2023 · cited 50× · PMID 36477733 · DOI 10.1038/s41591-022-02120-7
3. An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.
   Bansal G, Thanikachalam PV, Maurya RK, Chawla P, et al · · 2020 · cited 49× · PMID 32154036 · DOI 10.1016/j.jare.2020.01.008
4. Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study.
   Shields BM, Angwin CD, Shepherd MH, Britten N, et al · · 2023 · cited 11× · PMID 36477734 · DOI 10.1038/s41591-022-02121-6
5. 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 MASTER
   Angwin C, Jenkinson C, Jones A, Jennison C, et al · · 2020 · cited 10× · PMID 33371044 · DOI 10.1136/bmjopen-2020-042784
6. 58^th EASD Annual Meeting of the European Association for the Study of Diabetes : Stockholm, Sweden, 19 - 23 September 2022.
   · 2022 · cited 6× · PMID 35920845 · DOI 10.1007/s00125-022-05755-w
7. TriMaster: randomised double-blind crossover trial of a DPP4-inhibitor, SGLT2-inhibitor and thiazolidinedione to evaluate differential glycaemic response to therapy based on obesity and renal function
   Hattersley A, Shields B, Dennis J, Angwin C, et al · · 2022 · DOI 10.21203/rs.3.rs-2132634/v1