A 16 Weeks Study on Efficacy and Safety of Two Doses of Empagliflozin (BI 10773) (Once Daily Versus Twice Daily) in Patients With Type 2 Diabetes Mellitus and Preexisting Metformin Therapy

• Change in fasting plasma glucose from baseline [ Time Frame: week 1 and week 16 ] [ Designated as safety issue: No ]
• Change in fasting plasma glucose by visit over time [ Time Frame: up to 16 weeks ] [ Designated as safety issue: No ]
• Change in glycated hemoglobin by visit over time [ Time Frame: up to 16 weeks ] [ Designated as safety issue: No ]

The aim of this study is to investigate the efficacy and safety of two doses (high and low) of empagliflozin as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) and insufficient glycaemic control. Both doses may be given once daily or split to a twice daily dosage. This results in 4 different dosage regimens of empagliflozin (high dose once daily or split vs. low dose once daily or split). This is done to evaluate whether a twice daily dose regimen of empagliflozin results in a loss of efficacy relative to once daily dosing when given on top of metformin background therapy.

• Drug: Placebo
  Patients receive placebo matching empagliflozin (low dose qd)
• Drug: Placebo
  Patients receive placebo matching empagliflozin (low dose bid)
• Drug: Placebo
  Patients receive placebo matching Empagliflozin (high dose qd)
• Drug: empagliflozin (low dose qd)
  Patients receive Empagliflozin low dose once daily
• Drug: Placebo
  Patients receive placebo matching Empagliflozin (high dose bid)
• Drug: Empagliflozin (high dose qd)
  Patients receive Empagliflozin high dose once daily
• Drug: empagliflozin (high dose bid)
  Patients receive Empagliflozin high dose split twice daily
• Drug: empagliflozin (low dose bid)
  Patients receive Empagliflozin low dose split twice daily

• Experimental: empagliflozin (high dose qd)
  Patients receive Empagliflozin high dose once daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
  • Drug: Empagliflozin (high dose qd)
• Experimental: empagliflozin (high dose bid)
  Patients receive Empagliflozin high dose split twice daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
  • Drug: empagliflozin (high dose bid)
• Experimental: empagliflozin (low dose qd)
  Patients receive Empagliflozin low dose once daily
  Interventions:

  • Drug: empagliflozin (low dose qd)
  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
• Experimental: empagliflozin (low dose bid)
  Patients receive Empagliflozin low dose split twice daily
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
  • Drug: empagliflozin (low dose bid)
• Placebo Comparator: Placebo
  Patients receive placebo matching Empagliflozin
  Interventions:

  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo
  • Drug: Placebo

Inclusion criteria:

1. confirmed diagnosis of T2DM
2. Glycated hemoglobin (HbA1c) >=7.0 and <=10/0% at Visit 1
3. Metformin therapy (at least 1500 mg/day, BID)
4. age>=18 at Visit 1
5. body mass index <=45 kg/m2

Exclusion criteria:

1. estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) screening and/or run-in
2. a confirmed glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in