Safety and Efficacy of Empagliflozin (BI 10773) and Sitagliptin Versus Placebo Over 76 Weeks in Patients With Type 2 Diabetes

• Changes from baseline in clinical laboratory values, changes from baseline of Albumin/creatinine ratio and use of rescue therapy after 52, 76 weeks of treatment and at end of trial [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: Yes ]
• To investigate the long-term safety and tolerability of BI 10773. [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: Yes ]
• Incidence and intensity of adverse events, hypoglycaemic events, protocol-specified significant adverse events, cardiovascular events (Clinical Event Committee adjudication results) after 52, 76 weeks of treatment and at end of trial [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: Yes ]

• To assess efficacy of BI 10773 and for patients from 1245.20 sitagliptin for minimum 76 weeks compared to placebo as monotherapy or placebo on a background of pioglitazone or placebo on a background of metformin with or without sulfonylurea. [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: No ]
• The HbA1c, body weight (kg), waist circumference and fasting plasma glucose changes from baseline after 52, 76 weeks of treatment and to end of trial [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: No ]
• Composite endpoint of the following conditions after 52, 76 weeks of treatment and to end of trial change from baseline in (all three fulfilled): - HbA1c > 0.5% - systolic blood pressure > 3 mmHg - weight >2% [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: No ]
• Systolic and diastolic blood pressure: Change from baseline after 52, 76 weeks of treatment and to end of trial For patients rolling over from 1245.20: - Change from baseline in biomarkers of insulin sensitivity and secretion to end of trial [ Time Frame: Treatment period (minimum 76 weeks) ] [ Designated as safety issue: No ]

This study will investigate the efficacy and long term safety and tolerability of BI 10773 in type 2 diabetic patients.

• Drug: BI 10773
  BI 10773 tablets once daily
• Drug: Placebo
  Placebo matching BI 10773 low dose
• Drug: Placebo
  Placebo matching BI 10773 high dose
• Drug: Placebo
  Placebo matching Sitagliptin
• Drug: Sitagliptin 100mg
  Sitagliptin once daily

• Experimental: BI 10773 low (drug naive)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
  • Drug: Placebo
• Experimental: BI 10773 high (drug naive)
  BI 10773 tablets once daily
  Interventions:

  • Drug: Placebo
  • Drug: BI 10773
  • Drug: Placebo
• Placebo Comparator: Placebo (drug naive)
  Placebo tablets matching BI 10773 / Sitagliptin once daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
• Active Comparator: Sitagliptin 100mg (drug naive)
  Sitagliptin once daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Sitagliptin 100mg
• Experimental: BI 10773 low (pioglitazone)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
• Experimental: BI 10773 high (pioglitazone)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
• Placebo Comparator: Placebo (pioglitazone)
  Placebo tablets matching BI 10773 once daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
• Experimental: BI 10773 low (metformin)
  BI 10773 tablets once daily
  Interventions:

  • Drug: Placebo
  • Drug: BI 10773
• Experimental: BI 10773 high (metformin)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
• Placebo Comparator: Placebo (metformin)
  Placebo tablets matching BI 10773 once daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
• Experimental: BI 10773 low (metformin+sulfonylurea)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
• Experimental: BI 10773 high (metformin+sulfonylurea)
  BI 10773 tablets once daily
  Interventions:

  • Drug: BI 10773
  • Drug: Placebo
• Placebo Comparator: Placebo (metformin+sulfonylurea)
  Placebo tablets matching BI 10773
  Interventions:

  • Drug: Placebo
  • Drug: Placebo

Inclusion criteria:

1. Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy.
2. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation.

Exclusion criteria:

1. Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23.
2. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial.
3. Impaired renal function defined as glomerular filtration rate<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial.
4. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23
5. Pre-menopausal women (last menstruation < or = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
6. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.
7. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23).
8. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.