Efficacy and Safety of Empagliflozin (BI 10773) Versus Placebo and Sitagliptin Over 24 Weeks in Patients With Type 2 Diabetes

• Body weight: Change from baseline to week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Systolic and diastolic blood pressure (SBP and DBP): Change from baseline to week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

The aim of this study is to investigate the efficacy, safety and tolerability of BI 10773 compared to placebo and sitagliptin given for 24 weeks as monotherapy in patients with T2DM with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 10773 when given for 24 weeks in patients with T2DM with very poor glycaemic control.

• Drug: Placebo identical to BI10773 high dose
  placebo tablets once daily
• Drug: BI 10773
  BI 10773 low dose tablet once daily
• Drug: BI 10773 open label
  Patients receive BI 10773 high dose tablets open label once daily
• Drug: Placebo identical to BI10773 low dose
  placebo tablets once daily
• Drug: Placebo identical to Sitagliptin 100mg
  placebo tablets once daily
• Drug: BI10773
  BI 10773 high dose tablets once daily
• Drug: Sitagliptin
  Sitagliptin tablets 100 mg once daily

• Experimental: BI 10773 low dose
  Patients receive BI 10773 low dose tablets once daily
  Interventions:

  • Drug: Placebo identical to BI10773 high dose
  • Drug: BI 10773
  • Drug: Placebo identical to Sitagliptin 100mg
• Experimental: BI 10773 high dose
  Patients receive BI 10773 high dose tablets once daily
  Interventions:

  • Drug: Placebo identical to BI10773 low dose
  • Drug: BI10773
  • Drug: Placebo identical to Sitagliptin 100mg
• Placebo Comparator: Placebo
  Patients receive tablets identical to those containing BI 10773 low dose and high dose and to Sitagliptin
  Interventions:

  • Drug: Placebo identical to BI10773 low dose
  • Drug: Placebo identical to Sitagliptin 100mg
  • Drug: Placebo identical to BI10773 high dose
• Active Comparator: Sitagliptin 100 mg
  Patients receive Sitagliptin 100 mg tablets once daily
  Interventions:

  • Drug: Placebo identical to BI10773 high dose
  • Drug: Sitagliptin
  • Drug: Placebo identical to BI10773 low dose
• Experimental: BI 10773 high dose open label
  Patients receive BI 10773 high dose tablets open label once daily
  Intervention: Drug: BI 10773 open label

Inclusion criteria:

1. Diagnosis of type 2 diabetes mellitus prior to informed consent;
2. Male and female patients on diet and exercise regimen who are drug-naïve;
3. HbA1c >= 7.0% and <= 10.0% at Visit 1 (screening) for randomised treatment; HbA1c > 10.0% at visit 1 (screening) for the open-label BI 10773 arm;
4. Age >= 20 (Japan); Age >= 18 (countries other than Japan);
5. BMI <= 45 kg/m2 at Visit 1 (screening);
6. Signed and dated written informed consent by date of Visit 1

Exclusion criteria:

1. Uncontrolled hyperglycaemia;
2. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent;
3. Indication of liver disease, either ALT, AST, or alkaline phosphatase above 3 x ULN;
4. Impaired renal function (eGFR<50 ml/min);
5. Bariatric surgery within the past two years or other GI surgeries;
6. Medical history of cancer;
7. Contraindications to sitagliptin;
8. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell;
9. Treatment with any anti-diabetes drug within 12 weeks prior to randomisation;
10. Treatment with anti-obesity drugs or any other treatment leading to unstable body weight;
11. Current treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM;
12. Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and not practicing an acceptable method of birth control;
13. Alcohol or drug abuse;
14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial;
15. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial