Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes

• HbA1c Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
  Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.
• HbA1c Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
  Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.
• FPG Change From Baseline at Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
  Change from baseline reflects the Week 12 FPG minus the baseline FPG. Treatment means are adjusted for baseline HbA1c, baseline fasting plasma glucose and use of prior oral antidiabetics (OADs) in addition to background metformin.
• FPG Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
  Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.
• FPG Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
  Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.
• Percentage of Patients With HbA1c Lowering by 0.5% or More at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Percentage of Patients With Rescue Therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

The objective of the study is to investigate the efficacy and safety of linagliptin 2.5 mg twice daily compared to 5 mg once daily compared to placebo given orally for 12 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control. It is planned to show non-inferiority of linagliptin 2.5 mg twice daily compared to 5 mg once daily and each treatment's superiority over placebo.

• Drug: linagliptin low dose
  patient to receive tablets containing low dose linagliptin twice daily
• Drug: placebo
  patient to receive placebo tablet(s) matching linagliptin
• Drug: linagliptin medium dose
  patient to receive a tablet containing medium dose linagliptin once daily

• Experimental: linagliptin low dose
  linagliptin low dose twice daily
  Intervention: Drug: linagliptin low dose
• Placebo Comparator: placebo
  placebo matching linagliptin
  Intervention: Drug: placebo
• Experimental: linagliptin medium dose
  linagliptin medium dose once daily
  Intervention: Drug: linagliptin medium dose

Inclusion criteria

1. Diagnosis of type 2 diabetes mellitus.
2. Current treatment with metformin alone (>/= 1500 mg or maximally tolerated dose) or metformin plus 1 other antidiabetic drug. Metformin must be administered in twice daily dosing regimen. Patients taking metformin three times daily can be included if posology is switched to twice daily and total daily dose is maintained.
3. Glycosylated haemoglobin (HbA1c) is between 7.0% - 10.0%.
4. Body Mass Index (BMI) </=45 kg/m2.

Exclusion criteria

1. Treatment with extended release metformin.
2. Uncontrolled hyperglycaemia (fasting plasma glucose > 240 mg/dL or 13.3 mmol/L).
3. Myocardial infarction (MI), stroke or transient ischaemic attack (TIA) within 6 months prior to informed consent.
4. Impaired hepatic or renal function, or gastric bypass surgery.
5. Treatment with glitazones, glucagon like peptide-1 (GLP-1) analogues/mimetics, antiobesity agents, or insulin within 3 months of informed consent.
6. Current treatment with systemic steroids or change in dosage of thyroid hormones.
7. Alcohol or drug abuse within 3 months of informed consent.
8. Participation in another trial with investigational drug within 2 months prior to informed consent.
9. Pre-menopausal women who are nursing, pregnant or not practicing an acceptable method of birth control.