Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive Patients With Type 2 Diabetes

• Change from baseline in fasting plasma glucose (FPG) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change from baseline in body weight [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

This study will investigate the efficacy and safety of two doses (high and low) of empagliflozin in combination with metformin (500 mg and 1000 mg) administered twice daily in patients with type 2 diabetes mellitus (T2DM). Study will compare four dose combinations of empagliflozin + metformin versus each individual component after 24 weeks of treatment.

• Diabetes Mellitus, Type 2
• Hyperglycemia

• Drug: Metformin 500 mg bid
  Metformin 500 mg twice daily
• Drug: Metformin 1000 mg bid
  Metformin 1000 mg twice daily
• Drug: Empagliflozin low dose qd
  Empagliflozin low dose once daily
• Drug: Empagliflozin high dose qd
  Empagliflozin high dose once daily
• Drug: Empagliflozin low dose bid
  Empagliflozin low dose split twice daily
• Drug: Empagliflozin high dose bid
  Empagliflozin high dose split twice daily

• Experimental: Empagliflozin low dose qd
  Empagliflozin low dose once daily
  Intervention: Drug: Empagliflozin low dose qd
• Experimental: Empagliflozin high dose qd
  Empagliflozin high dose once daily
  Intervention: Drug: Empagliflozin high dose qd
• Experimental: OL empa high dose + met 1000 mg bid
  Open label empagliflozin high dose split twice daily + metformin 1000 mg twice daily - Patients are no longer enrolled into this arm because of change in the inclusion criteria in protocol version 2.0 all patients are now enrolled into remaining double-blind arms. Patients already enrolled in the open-label arm according to protocol version 1.0 can complete the study.
  Interventions:

  • Drug: Metformin 1000 mg bid
  • Drug: Empagliflozin high dose bid
• Experimental: Empagliflozin low dose + met 500 mg bid
  Empagliflozin low dose split twice daily + metformin 500 mg twice daily
  Interventions:

  • Drug: Metformin 500 mg bid
  • Drug: Empagliflozin low dose bid
• Experimental: Empagliflozin low dose + met 1000 mg bid
  Empagliflozin low dose split twice daily + metformin 1000 mg twice daily
  Interventions:

  • Drug: Empagliflozin low dose bid
  • Drug: Metformin 1000 mg bid
• Experimental: Empagliflozin high dose + met 500 mg bid
  Empagliflozin high dose split twice daily + metformin 500 mg twice daily
  Interventions:

  • Drug: Metformin 500 mg bid
  • Drug: Empagliflozin high dose bid
• Experimental: Empagliflozin high dose + met 1000mg bid
  Empagliflozin high dose split twice daily + metformin 1000 mg twice daily
  Interventions:

  • Drug: Metformin 1000 mg bid
  • Drug: Empagliflozin high dose bid
• Experimental: Metformin 500 mg bid
  Metformin 500 mg twice daily
  Intervention: Drug: Metformin 500 mg bid
• Experimental: Metformin 1000 mg bid
  Metformin 1000 mg twice daily
  Intervention: Drug: Metformin 1000 mg bid

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-naive, defined as absence of any oral antidiabetic therapy for 12 weeks prior to randomization
3. HbA1c >=7.5% and <= 12% (>=58.5 mmol/mol and <=107.7 mmol/mol)
4. Body Mass Index (BMI) <= 45 kg/m2 at screening

Exclusion criteria:

1. Uncontrolled hyperglycemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second laboratory measurement (not on the same day)
2. Any antidiabetic drug within 12 weeks prior to randomization
3. Impaired renal function, defined as estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) as determined during screening and/or run-in period
4. Contraindications to metformin according to the local label