Type 2 Diabetes Mellitus MedDRA version: 9.1 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Female and/or male aged =18 years and =79 years at the time of consenting 3. Diagnosed with type 2 diabetes 4. Inadequate glycaemic control, defined as HbA1c >7% and =10.5% 5. Ongoing treatment with metformin alone on a stable dose of =1500 mg/day for at least 8 weeks prior to enrolment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diagnosis of Type 1 diabetes mellitus, MODY, or secondary diabetes mellitus 2. Insulin therapy within 24 weeks of enrolment (with the exception of insulin use during a hospitalization or during pregnancy in a patient with gestational diabetes) 3. History of diabetes insipidus 4. History of diabetic ketoacidosis or other acute or chronic metabolic acidosis 5. Symptoms of poorly controlled diabetes including, but not limited to, marked polyuria, polydipsia and/or greater than 10% weight loss during the 3 months prior to enrolment 6. Previous treatment with a DPP-4 inhibitor 7. BMI >45 kg/m2 8. History of unstable or rapidly progressing renal disease 9. Known condition of congenital renal glucosuria 10. History of severe hepatobiliary disease or hepatotoxicicty with any medication 11. Pregnant or breastfeeding patients 12. Treatment with glucocorticoids equivalent to oral prednisolone >10 mg (betametasone >1.2 mg/dexamethasone >1.5 mg/hydrocortisone >40 mg)/day within 30 days prior to enrolment; topical or inhaled corticosteroids are allowed 13. History of bariatric surgery 14. Administration of weight loss medication, including but not limited to sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days prior to enrolment 15. Treatment for Human Immunodeficiency Virus (HIV)/use of antiviral drugs (delavirdine, indinavir, nelfinavir, ritonavir, saquinavir) and/or known immunocompromised status, including patients who have undergone organ transplantation 16. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV (see Appendix D), unstable congestive heart failure and/or left ventricular ejection fraction of = 40% 17. Significant cardiovascular history within the past 6 months prior to the screening visit, defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident 18. Severe respiratory failure or severe emphysema 19. Systolic BP =180 mmHg and/or diastolic BP =110 mmHg 20. Any clinically significant abnormality identified on physical examination, ECG or laboratory tests, which in the judgement of the investigator would compromise the patient’s safety or successful participation in the clinical study 21. Treatment with unstable doses of teriparatide, bisphosphonates and/or calcitonin (Note: teriparatide, bisphosponates and/or calcitonin are allowed provided the dose has not changed within 30 days prior to enrolment) 22. Patients who, in the judgment of the investigator, may be at risk for dehydration 23. History of chronic haemolytic anemia or haemoglobinopathies (sickle cell anemia or thalassemias, sideroblatic anaemia) 24. History of drug-induced liver enzyme elevations 25. History of drug-induced myopathy or drug-induced CK elevation 26. Acute or chronic metabolic acidosis 27. History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma 28. History of alcohol abuse or illegal drug abuse within the past 12 months 29. Intolerance, contraindication or potential allergy to dapagliflozin, metformin, sitagliptin, glimepiride, other sulfonylurea, placebo or formulation excipients 30. Suspected or confirmed poor protocol or medication compliance as judged by the investigator 31. Donation or transfusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine whether, after 24 weeks of oral administration of double-blind treatment, the change from baseline in glycosylated haemoglobin A1c (HbA1c) level with dapagliflozin 10 mg plus metformin is non-inferior to sitagliptin (DPP-4 inhibitor) 100 mg plus metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone. ;Secondary Objective: Key secondary objectives: -To show that dapagliflozin plus metformin reduces body weight compared to sitagliptin plus metformin from baseline to week 24 -To show that dapagliflozin plus metformin reduces body weight compared to sitagliptin plus metformin from baseline to week 24 in patients with baseline Body Mass Index (BMI) >= 27 kg/m2 -To show that dapagliflozin plus metformin decreases seated systolic blood pressure (SBP) compared to sitagliptin plus metformin from baseline to week 6 in patients with baseline SBP =130 mmHg -To show that dapagliflozin plus metformin reduces fasting plasma glucose compared to sitagliptin plus metformin after 1 week of treatment.;Primary end point(s): Change in HbA1c from baseline to week 24 | — |
Countries
Austria, Czech Republic, Germany, Slovakia, United Kingdom
Outcome results
None listed