Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes

A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (One Dose, e.g. 5 mg), Administered Orally Once Daily Over 24 Weeks, With an Open Label Extension to 80 Weeks (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control

Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug

2. Diagnosis of type 2 diabetes prior to informed consent

3. Glycosylated haemoglobin A1 (HbA1c)at screening:

   For patients undergoing wash out of previous medication: HbA1c 6.5 - 9.0% For patients not undergoing wash-out of previous medication: HbA1c 7.0 - 10.0%

4. Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at the beginning of Placebo Run-in

5. Age 18 -80 years

6. BMI (Body Mass Index) less than 40 kg/m2

7. Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent

2. Impaired hepatic function

3. Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo

4. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent

5. Treatment with an injectable GLP-1 analogue (e.g. exenatide) within 3 months prior to informed consent

6. Treatment with insulin within 3 months prior to informed consent

7. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent

8. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse

9. Participation in another trial with an investigational drug within 2 months prior to informed consent

10. Pre-menopausal women 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.

11. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.

12. Renal failure or renal impairment

13. Unstable or acute congestive heart failure

14. Acute or chronic metabolic acidosis (present in patient history)

15. Hereditary galactose intolerance