A 24-Week, International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III study to Evaluate the Efficacy and Safety of Dapagliflozin in Combination with Metformin compared with a DPP-4 inhibitor (Sitagliptin) in Combination with Metformin in Adult Patients with Type 2 Diabetes who have Inadequate Glycaemic Control on Metformin Therapy Alone

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 494

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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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