TriMaster: Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes.

• Status: Completed
• Trial end date: 2021-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NIHR Exeter Clinical Research Facility; Royal Devon and Exeter NHS Foundation Trust
• Collaborators: King's College London; Newcastle University; NHS Tayside; Royal Devon and Exeter NHS Foundation Trust; University of Dundee; University of Exeter; University of Glasgow
• Treatments: 2,4-thiazolidinedione; Canagliflozin; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• Clinical diagnosis of Type 2 diabetes

• Age ≥30 and ≤80

• Currently treated with 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 ≥12months

• No change in diabetes treatment (new treatments or dose change) within previous 3 months

• HbA1c > 58mmol/mol (7.5%) and ≤110mmol/mol (12.2%) - confirmed at screening visit

• eGFR ≥ 60mls/min/1.73m² - confirmed at screening visit

• Able and willing to give informed consent

Exclusion Criteria:

• Changes in glucose-lowering therapy or dose within last 3 months

• HbA1c ≤ 58mmol/mol (7.5%) or >110mmol/mol (12.2%)

• eGFR <60mls/min/1.73m².

• Diabetes duration <12 months

• ALT >2.5 x upper limit of the assay normal range or known liver disease, specifically >30 μmol/L that is associated with other evidence of liver failure.

• Insulin treated within the last 12 months

• Limb ischaemia shown by absence of both pulses in one or both feet.

• Currently treated with corticosteroids

• Currently treated with rifampicin, gemfibrozil, phenytoin and carbamazepine

• Active infection (any infection requiring antibiotics at present)

• Foot ulcer requiring antibiotics within previous three months

• Recent (within 3 months) significant surgery or planned surgery (excluding minor procedures)

• Acute cardiovascular episode (angina, myocardial infarction, stroke, transient ischemic episode) occurring within the previous 3 months

• History of heart failure

• Current use of loop diuretic therapy (Furosemide or Bumetanide)

• History of bladder carcinoma

• Current/ongoing investigation for macroscopic haematuria

• History of Diabetic Ketoacidosis

• History of pancreatitis

• Pregnant, breastfeeding or planning a pregnancy over the study period

• Concurrent Participation on another Clinical Trial of an Investigational Medicinal Product, where the IMP is currently being taken, or without sufficient washout period* and without consultation with the CTIMP research team.

• Unable or unwilling to give informed consent

• Sufficient washout period = five times the half-life of the IMP / potential IMP if involving a placebo / longest half-life if a trial includes more than one drug