Efficacy and Safety of BI 1356 in Combination With Metformin in Patients With Type 2 Diabetes

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
There were in total 1560 patients randomised in the study. Of these, 1 patient was not treated. The remaining 8 patients not accounted for in the treated set were removed from all study analyses (explained in trial report) due to major good-clinical-practice violations at the site, and the inability to verify the validity of any patient level data.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Linagliptin	Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride	Patients randomized to receive Glimepiride 1-4mg and metformin

Participant Flow:   Overall Study

	Linagliptin	Glimepiride
STARTED	776 [1]	775 [2]
COMPLETED	587 [3]	604 [3]
NOT COMPLETED	189	171
Lack of Efficacy	45	15
Adverse Event	61	90
Protocol Violation	12	5
Lost to Follow-up	11	13
Withdrawal by Subject	27	24
Other reason (not specified)	33	24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Linagliptin	Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride	Patients randomized to receive Glimepiride 1-4mg and metformin
Total	Total of all reporting groups

Baseline Measures

	Linagliptin	Glimepiride	Total
Overall Participants Analyzed  [Units: Participants]	776	775	1551
Age  [Units: Years] Mean (Standard Deviation)	59.8  (9.4)	59.8  (9.4)	59.8  (9.4)
Gender  [Units: Patients]
Female	314	304	618
Male	462	471	933
Body mass index (BMI) continuous  [Units: Kg/m^2] Mean (Standard Deviation)	30.21  (4.77)	30.31  (4.57)	30.26  (4.67)
Weight  [Units: Kg] Mean (Standard Deviation)	86.14  (17.57)	86.77  (16.69)	86.46  (17.14)
Glycosylated haemoglobin (HbA1c) [1]  [Units: Percent] Mean (Standard Deviation)	7.69  (0.88)	7.69  (0.86)	7.69  (0.87)
[1] Baseline HbA1c was available for 1519 patients in the Full Analysis Set (FAS), 764 treated with Linagliptin and 755 patients treated with Glimepiride.
Fasting blood plasma glucose (FPG) [1]  [Units: mg/dL] Mean (Standard Deviation)	164.46  (42.83)	166.09  (42.05)	165.27  (42.43)
[1] Baseline fasting plasma glucose (FPG) was available for 1475 patients in the FAS, 740 treated with Linagliptin and 735 patients treated with Glimepiride.

1.  Primary:

HbA1c Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

2.  Primary:

HbA1c Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

3.  Secondary:

Body Weight Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

4.  Secondary:

Body Weight Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

5.  Secondary:

Incidence of Hypoglycaemic Events up to 52 Weeks   [ Time Frame: Week 52 ]

6.  Secondary:

Incidence of Hypoglycaemic Events up to 104 Weeks   [ Time Frame: Week 104 ]

7.  Secondary:

Fasting Plasma Glucose (FPG) Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]

8.  Secondary:

Fasting Plasma Glucose (FPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

9.  Secondary:

Percentage of Patients With HbA1c <7.0% at Week 52   [ Time Frame: Week 52 ]

10.  Secondary:

Percentage of Patients With HbA1c <7.0% at Week 104   [ Time Frame: Week 104 ]

11.  Secondary:

Percentage of Patients With HbA1c <6.5% at Week 52   [ Time Frame: Week 52 ]

12.  Secondary:

Percentage of Patients With HbA1c <6.5% at Week 104   [ Time Frame: Week 104 ]

13.  Secondary:

Percentage of Patients With HbA1c Lowering by 0.5% at Week 104   [ Time Frame: Week 104 ]

14.  Secondary:

2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]

15.  Secondary:

HbA1c Change at Week 4   [ Time Frame: Baseline and week 4 ]

16.  Secondary:

HbA1c Change at Week 8   [ Time Frame: Baseline and week 8 ]

17.  Secondary:

HbA1c Change at Week 12   [ Time Frame: Baseline and week 12 ]

18.  Secondary:

HbA1c Change at Week 16   [ Time Frame: Baseline and week 16 ]

19.  Secondary:

HbA1c Change at Week 28   [ Time Frame: Baseline and week 28 ]

20.  Secondary:

HbA1c Change at Week 40   [ Time Frame: Baseline and week 40 ]

21.  Secondary:

HbA1c Change at Week 52   [ Time Frame: Baseline and week 52 ]

22.  Secondary:

HbA1c Change at Week 65   [ Time Frame: Baseline and week 65 ]

23.  Secondary:

HbA1c Change at Week 78   [ Time Frame: Baseline and week 78 ]

24.  Secondary:

HbA1c Change at Week 91   [ Time Frame: Baseline and week 91 ]

25.  Secondary:

HbA1c Change at Week 104   [ Time Frame: Baseline and week 104 ]

26.  Secondary:

Change in Baseline Lipid Parameter Cholesterol at Week 104   [ Time Frame: Baseline and week 104 ]

27.  Secondary:

Change in Baseline Lipid Parameter HDL at Week 104   [ Time Frame: Baseline and week 104 ]

28.  Secondary:

Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104   [ Time Frame: Baseline and week 104 ]

29.  Secondary:

Change in Baseline Lipid Parameter Triglyceride at Week 104   [ Time Frame: Baseline and week 104 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
With the exception of HbA1c<6.5% and HbA1c<7.0% at Week52, all other endpoints are presented in the Week52 repeated analysis within the final clinical trial report, where discrepancies between interim and final results are also explained.