A Phase 4 interventional study of Sitagliptin - DPP4i and Canagliflozin - SGLT2i in Type 2 Diabetes, sponsored by Royal Devon and Exeter NHS Foundation Trust. Completed at 1 site in United Kingdom. Open to participants aged 30 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-04-01.
Sponsored by Royal Devon and Exeter NHS Foundation Trust · Phase 4, Interventional, and Treatment
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.
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.
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 525 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
Browse Diabetes Mellitus studies →Royal Devon and Exeter NHS Foundation Trust is the lead sponsor of 62 studies on the registry; 8 are open to participants now.
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Exclusion Criteria:
Unable or unwilling to give informed consent
Drug: Sitagliptin - DPP4i
Drug: Canagliflozin - SGLT2i
Drug: Pioglitazone - TZD
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.
Also known as: Januvia
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.
Also known as: Invokana
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.
Also known as: Actos
On treatment HbA1c in obese patients (BMI >30kgm-2), compared to non-obese patients
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.
Time frame: 16 weeks
On treatment HbA1c in patients with an eGFR <90 mls/min/1.73m2 compared to patients with an eGFR >90 mls/min/1.73m2.
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 efficacy. 2. Respond well to sitagliptin, a DPP4i that is renally cleared, as the reduced eGFR will increase plasma DPP4i concentrations.
Time frame: 16 weeks
Patient preference
Patient treatment preference of study drug within hypothesised strata and overall
Time frame: 48-54 weeks (3 x 16 weeks of therapy)
Prevalence of side effects
Prevalence of side effects within hypothesised strata and for specific drugs, to include: weight gain, hypoglycaemia, oedema, genital tract infection and discontinuation of therapy
Time frame: 48-54 weeks (3 x 16 weeks of therapy)
HbA1c on therapy against predefined test of gender heterogeneity
Predefined test of gender heterogeneity with pilot data suggesting females are likely to show an improved response relative to males for pioglitazone.
Time frame: 16 weeks
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This study is completed, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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Royal Devon and Exeter NHS Foundation Trust