TriMaster: Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes.
Summary
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.
Timeline
- Start
- 2016-11-01
- Primary completion
- 2021-01
- Completion
- 2021-01
Outcome
Met primary endpoint
paper had a 2.88 mmol/mol (95% confidence interval (CI): 0.98, 4.79) lower HbA1c on pioglitazone than on sitagliptin (n = 356, P = 0.003). PMID 36477733 ↗
paper had a 2.90 mmol/mol (95% CI: 1.19, 4.61) lower HbA1c on sitagliptin than on canagliflozin (n = 342, P = 0.001). PMID 36477733 ↗
Publications
- Shields BM, Angwin CD, Shepherd MH, Britten N, Jones AG, Sattar N, Holman R, Pearson ER, Hattersley AT. Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study. Nat Med. 2023 Feb;29(2):384-391. doi: 10.1038/s41591-022-02121-6. Epub 2022 Dec 7.
- Shields BM, Dennis JM, Angwin CD, Warren F, Henley WE, Farmer AJ, Sattar N, Holman RR, Jones AG, Pearson ER, Hattersley AT; TriMaster Study group. Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study. Nat Med. 2023 Feb;29(2):376-383. doi: 10.1038/s41591-022-02120-7. Epub 2022 Dec 7.
- Angwin C, Jenkinson C, Jones A, Jennison C, Henley W, Farmer A, Sattar N, Holman RR, Pearson E, Shields B, Hattersley A; MASTERMIND consortium. 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. 2020 Dec 21;10(12):e042784. doi: 10.1136/bmjopen-2020-042784.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | CANAGLIFLOZIN ANHYDROUS | Small molecule | 100 mg | Oral |
| Subject | Pioglitazone | Small molecule | 30 mg | Oral |
| Subject | Sitagliptin | Small molecule | 100 mg | Oral |