Specialty: Diabetes, Primary sub-specialty: Type 2
Conditions
Interventions
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 dapaglifloz
Screening Assessment (~1 hour) at Clinical Sciences, Aintree University Hospital:
This is an initial Screening Visit to determine eligibility to take part in the trial which lasts for 32 weeks. Partic
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females, age 18-65 years 2. A clinical diagnosis of type 2 diabetes 3. Glycosylated haemoglobin (HbA1c) =6.5% but =11% (48-97mmol/mol) 4. Currently treated with either diet or any combination of metformin, DPPIV inhibitors* and sulphonylureas (excluding patients treated with pioglitazone or insulin). *DPP-IV inhibitors will require wash out period of four weeks 5. BMI 30-50 kg/m2 6. Patients who are receiving the following medications must be on stable treatment regimen for a minimum of 2 months prior to screening: 7. Thyroid hormone replacement 8. Antidepressants
Exclusion criteria
Exclusion criteria: 1. Type 1 diabetes mellitus 2. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma 3. Renal impairment: eGFR less than 60 ml/minute/1.73m2 4. Hyperthyroidism 5. Hypothyroidism (subjects with a normal TSH and free T4, and on a stable dose of thyroxine for at least 3 months may be included) 6. Uncontrolled hypertension (SBP >160mmHg/DBP >110mmHg) 7. Congestive heart failure class III-IV 8. Recent ( 3 x ULN 20. AST > 3 x ULN 21. Bilirubin > 2 x ULN 22. Haemoglobin = 10.5 g/dL (= 105 g/L) for men; haemoglobin = 9.5 g/dL (= 95 g/L) for women 23. eGFR 150kg (due to MRI limitations) 26. BMI 50 kg/m2 27. Recent major change in body weight (> 3kg loss or gain in preceding month) Subjects with a history of any serious hypersensitivity reaction to GLP1-RA or SGLT2 inhibitor 28. Participant should have no allergies against metacresol (the preservative in insulin vial) 29. History of anaphylaxis to food 30. Known food allergies or food intolerance 31. Known hypersensitivity to heparin 32. Known hypersensitivity to IV catheter equipment 33. Females of childbearing age who are not using adequate contraceptive methods or who are planning a pregnancy in the next 6 months 34. Women who are pregnant or breastfeeding 35. Diabetes treated with pioglitazone, SGLT2 inhibitors, GLP-1 analogues or insulin, 36. Use of other weight loss medication or any drug that might affect body weight or appetite (including antipsychotics, orlistat or corticosteroids) 37. Patients who are currently receiving a loop diuretic that cannot be discontinued 38. Active or previous substance abuse or dependence 39. Prisoners or subjects who are involuntarily incarcerated 40. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome is measure by adjusted mean change in total body fat mass from baseline to week 32 quantified by DEXA. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Metabolic measures are measured using HbA1c (the principal measure of glycaemic control), 24 hour urinary glucose excretion and 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 using visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and Liver fat 4. Changes in cardiovascular function using indices of myocardial systolic and diastolic function using transthoracic echocardiography (Tissue Doppler Imaging) and endothelial function: Flow mediated dilatation will be measured in response to an ischaemic stimulus using brachial ultrasound | — |
Countries
England, United Kingdom
Contacts
Public ContactDaniel Cuthbertson
Outcome results
None listed