Type 2 Diabetes Mellitus MedDRA version: 19.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Dapagliflozin 10mg filmcoated tablet
Product Name: Dapagliflozin (BMS512148) 10mg filmcoated tablet
Product Code: EU/1/12/795/002
EU/1/12/795/007
Pharmaceutical Form: Tablet
INN or Proposed INN: dapagliflozin propanediol monohydrate
CAS Number: 461432-26-8
Other descriptive name: Forxiga
Concentration unit: mg milligram(s)
Conc
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The inclusion criterion for this trial includes: • • Males or females, age 18-65 years, • A clinical diagnosis of type 2 diabetes, • Glycosylated haemoglobin (HbA1c) >6.5% but =65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: The exclusion criterion for this trial includes: • Type 1 diabetes mellitus, • History of diabetic ketoacidosis or hyperosmolar non-ketotic coma, • Renal impairment: eGFR less than 60 ml/minute/1.73m2, • Hyperthyroidism, • Hypothyroidism (subjects with a normal TSH and free T4, and on a stable dose of thyroxine for at least 3 months may be included), • Uncontrolled hypertension (SBP >160mmHg/DBP >110mmHg), • Congestive heart failure class III-IV, • Recent ( 3 x ULN • AST > 3 x ULN • Bilirubin > 2 x ULN • Haemoglobin = 10.5 g/dL (= 105 g/L) for men; haemoglobin = 9.5 g/dL (= 95 g/L) for women • eGFR 150kg (due to MRI limitations) • BMI 50 kg/m2 • Recent major change in body weight (> 3kg loss or gain in preceding month) Allergies and Adverse Drug Reactions • Subjects with a history of any serious hypersensitivity reaction to GLP1-RA or SGLT2 inhibitor, • Participant should have no allergies against metacresol (the preservative in insulin vial), • History of anaphylaxis to food, • Known food allergies or food intolerance, • Known hypersensitivity to heparin, • Known hypersensitivity to IV catheter equipment. Sex and Reproductive Status • Females of childbearing age who are not using adequate contraceptive methods or who are planning a pregnancy in the next 6 months, • Women who are pregnant or breastfeeding. Prohibited Treatments and/or Therapies • Diabetes treated with pioglitazone, SGLT2 inhibitors, GLP-1 analogues or insulin, • Use of other weight loss medication or any drug that might affect body weight or appetite (including antipsychotics, orlistat or corticosteroids), • Patients who are currently receiving a loop diuretic that cannot be discontinued. Other Exclusion Criteria • Active or previous substance abuse or dependence, • Prisoners or subjects who are involuntarily incarcerated, • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the adjusted mean reduction in total body fat mass from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo).;Secondary Objective: The key secondary objectives of this trial are to assess the adjusted mean change from baseline in: 1. Metabolic measures • HbA1c (the principal measure of glycaemic control). • 24 hour urinary glucose excretion • Hepatic glucose output, measured using hyperinsulinaemic, euglycaemic clamp and stable isotope infusions of 2H-glucose. 2. Measures of food intake, feeding behaviour and appetite using test meal study days. 3. Changes in body weight and fat volume and distribution using MRI/MRS • Visceral adipose tissue (VAT), • Subcutaneous adipose tissue (SAT) and • Liver fat 4. Changes in cardiovascular function • Indices of myocardial systolic and diastolic function using transthoracic echocardiography (Tissue Doppler Imaging) • Endothelial function: Flow mediated dilatation will be measured in response to an ischaemic stimulus using brachial ultrasound ;Primary end point(s): The primary objective of the study is to compare the adjusted mean reduction in total body fat mass from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo).;Timepoint(s) of evaluation of this end point: End of treatment (32 weeks of treatment) for each patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Metabolic measures - HbA1c (the principal measure of glycaemic control) - 24 hour urinary glucose excretion - Hepatic glucose output, measured using hyperinsulinaemic, euglycaemic clamp and stable isotope infusions of 2H-glucose. 2. Measures of food intake, feeding behaviour and appetite using test meal study days 3. Changes in body weight and fat volume and distribution using MRI/MRS - Visceral adipose tissue (VAT) - Subcutaneous adipose tissue (SAT) - Liver fat 4. Changes in cardiovascular function - Indices of myocardial systolic and diastolic function using transthoracic echocardiography (Tissue Doppler Imaging) - Endothelial function: Flow mediated dilatation will be measured in response to an ischaemic stimulus using brachial ultrasound ;Timepoint(s) of evaluation of this end point: End of treatment (32 weeks of treatment) for each patient | — |
Countries
United Kingdom
Outcome results
None listed