TriMaster: Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes.
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      The study is a phase 4 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.

      600 patients aged 30-80 who have been on stable doses of 2 classes of therapy (not including
      the trial IMPs or GLP1-agonist) for at least 3 months with HbA1c >58mmol/mol (7.5%) will
      receive three double-blinded third-line non-injectable therapies. On recruitment into the
      study participants will have underlying pathophysiology assessed in a mixed-meal tolerance
      test (MMTT) and samples will be collected for baseline analysis and storage for future
      biomarker analysis and discovery. Participants will then receive 16 weeks of each
      over-encapsulated blinded therapy in random order.

      At the end of each treatment period, fasting blood will be taken to measure glycaemic
      response (HbA1c), fasting glucose and insulin concentrations trough drug levels and to
      confirm continued eligibility. Weight, blood pressure and. data about patient experience will
      also be collected including perceived side effects, preparedness to remain on therapy,
      psychological health and health related quality of life.

      At the end of the study, patient treatment preference will be recorded after feeding back to
      the patient for each of the 3 therapies their HbA1c, weight change, frequency of
      hypoglycaemias, any patient reported side effects and the patient's verdict on each therapy
      will be recorded. Each participant will be asked which treatments they would take long term
      and the reason for their preference.
    

Intervention name(s): Sitagliptin - DPP4i; Canagliflozin - SGLT2i; Pioglitazone - TZD
Intervention type(s): Drug; Drug; Drug
Intervention description(s): DPP4 inhibitor 100mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.; SGLT2 inhibitor 100mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.; Thiazolidinedione 30mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.
Other intervention name(s): Januvia; Invokana; Actos
Intervention MeSH terms: Pioglitazone; Sitagliptin Phosphate; Canagliflozin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Type 2 diabetes; Stratification; Biomarkers; Pharmacogenetics; SGLT2 inhibitors; Thiazolidinediones; DPP4 inhibitors