Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5.0 mg daily) compared to glimepiride given for 104 weeks as add-on therapy to preferably \> 1500 mg metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control
Interventions
DRUGPlacebo identical to BI 1356 5mg
Placebo tablet once daily
DRUGPlacebo identical to Glimepiride 1mg or 2mg or 3mg or 4 mg
Placebo tablets once daily
DRUGBI 1356
5mg, once daily in the morning for 104 weeks
DRUGGlimepiride
1mg or 2mg or 3mg or 4mg in the morning for 104 weeks
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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 one other oral antidiabetic drug 2. Glycosylated haemoglobin (HbA1c) 6.0 - 9.0% at screening for patients treated with metformin and one other oral antidiabetic drug 3. HbA1c 6.5 - 10.0% at screening for patients treated with metformin alone 4. HbA1c 6.5 - 10.0% at beginning of the placebo run-in phase
Exclusion criteria
1. Myocardial infarction, stroke or transient ischemic attack (TIA) 2. Impaired hepatic function 3. Renal failure or renal impairment 4. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening 5. Treatment with insulin or glucagon-like peptide 1 (GLP-1) analogue/antagonists within 3 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline at Week 104 | Baseline and week 104 | This co-primary endpoint, change from baseline, reflects the Week 104 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications. |
| HbA1c Change From Baseline at Week 52 | Baseline and week 52 | This co-primary endpoint, change from baseline, reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Hypoglycaemic Events up to 52 Weeks | Week 52 | A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a home blood glucose monitoring (HBGM) of below 55 mg/dl (3.1 mmol/L) |
| Incidence of Hypoglycaemic Events up to 104 Weeks | Week 104 | A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a HBGM of below 55 mg/dl (3.1 mmol/L) |
| Fasting Plasma Glucose (FPG) Change From Baseline at Week 52 | Baseline and week 52 | This change from baseline reflects the Week 52 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and the number of previous anti-diabetic medications. |
| Fasting Plasma Glucose (FPG) Change From Baseline at Week 104 | Baseline and week 104 | This change from baseline reflects the Week 104 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and number of previous anti-diabetic medications. |
| Percentage of Patients With HbA1c <7.0% at Week 52 | Week 52 | The percentage of patients with an HbA1c value below 7.0% at week 52, based upon patients with baseline HbA1c \>= 7%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c \>= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications. |
| Percentage of Patients With HbA1c <7.0% at Week 104 | Week 104 | The percentage of patients with an HbA1c value below 7.0% at week 104, based upon patients with baseline HbA1c \>= 7%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c \>= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications. |
| Percentage of Patients With HbA1c <6.5% at Week 52 | Week 52 | The percentage of patients with an HbA1c value below 6.5% at week 52, based upon patients with baseline HbA1c \>= 6.5%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c \>= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications. |
| Percentage of Patients With HbA1c <6.5% at Week 104 | Week 104 | The percentage of patients with an HbA1c value below 6.5% at week 104, based upon patients with baseline HbA1c \>= 6.5%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c \>= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications. |
| Percentage of Patients With HbA1c Lowering by 0.5% at Week 104 | Week 104 | Occurrence of relative efficacy response, defined as a lowering of 0.5% HbA1c at week 104 |
| 2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104 | Baseline and week 104 | This change from baseline reflects the Week 104 2 hr PPG minus the Baseline 2hr PPG. Means are treatment adjusted for baseline HbA1c, baseline 2hr PPG and number of previous anti-diabetic medications. |
| HbA1c Change at Week 4 | Baseline and week 4 | Difference of base percent value \[Week x(%) - baseline (%)\] |
| HbA1c Change at Week 8 | Baseline and week 8 | — |
| Body Weight Change From Baseline at Week 52 | Baseline and week 52 | This key secondary endpoint, change from baseline, reflects the Week 52 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications. |
| HbA1c Change at Week 16 | Baseline and week 16 | — |
| HbA1c Change at Week 28 | Baseline and week 28 | — |
| HbA1c Change at Week 40 | Baseline and week 40 | — |
| HbA1c Change at Week 52 | Baseline and week 52 | — |
| HbA1c Change at Week 65 | Baseline and week 65 | — |
| HbA1c Change at Week 78 | Baseline and week 78 | — |
| HbA1c Change at Week 91 | Baseline and week 91 | — |
| HbA1c Change at Week 104 | Baseline and week 104 | The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement available during the first phase of the study. Last observation carried forward (LOCF) was used as imputation rule. |
| Change in Baseline Lipid Parameter Cholesterol at Week 104 | Baseline and week 104 | — |
| Change in Baseline Lipid Parameter HDL at Week 104 | Baseline and week 104 | — |
| Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104 | Baseline and week 104 | — |
| Change in Baseline Lipid Parameter Triglyceride at Week 104 | Baseline and week 104 | — |
| HbA1c Change at Week 12 | Baseline and week 12 | — |
| Body Weight Change From Baseline at Week 104 | Baseline and week 104 | This key secondary endpoint, change from baseline, reflects the Week 104 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications. |
Countries
Bulgaria, Denmark, France, Germany, Hong Kong, Hungary, India, Ireland, Italy, Netherlands, Norway, Poland, South Africa, Sweden, United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Linagliptin Patients randomized to receive Linagliptin 5mg and metformin | 776 |
| Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin | 775 |
| Total | 1,551 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 61 | 90 |
| Overall Study | Lack of Efficacy | 45 | 15 |
| Overall Study | Lost to Follow-up | 11 | 13 |
| Overall Study | Other reason (not specified) | 33 | 24 |
| Overall Study | Protocol Violation | 12 | 5 |
| Overall Study | Withdrawal by Subject | 27 | 24 |
Baseline characteristics
| Characteristic | Glimepiride | Linagliptin | Total |
|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 9.4 | 59.8 Years STANDARD_DEVIATION 9.4 | 59.8 Years STANDARD_DEVIATION 9.4 |
| Body mass index (BMI) continuous | 30.31 kg/m^2 STANDARD_DEVIATION 4.57 | 30.21 kg/m^2 STANDARD_DEVIATION 4.77 | 30.26 kg/m^2 STANDARD_DEVIATION 4.67 |
| Fasting blood plasma glucose (FPG) | 166.09 mg/dL STANDARD_DEVIATION 42.05 | 164.46 mg/dL STANDARD_DEVIATION 42.83 | 165.27 mg/dL STANDARD_DEVIATION 42.43 |
| Glycosylated haemoglobin (HbA1c) | 7.69 Percent STANDARD_DEVIATION 0.86 | 7.69 Percent STANDARD_DEVIATION 0.88 | 7.69 Percent STANDARD_DEVIATION 0.87 |
| Sex: Female, Male Female | 304 Participants | 314 Participants | 618 Participants |
| Sex: Female, Male Male | 471 Participants | 462 Participants | 933 Participants |
| Weight | 86.77 kg STANDARD_DEVIATION 16.69 | 86.14 kg STANDARD_DEVIATION 17.57 | 86.46 kg STANDARD_DEVIATION 17.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 438 / 776 | 526 / 775 |
| serious Total, serious adverse events | 135 / 776 | 162 / 775 |
Outcome results
Primary
HbA1c Change From Baseline at Week 104
This co-primary endpoint, change from baseline, reflects the Week 104 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications.
Time frame: Baseline and week 104
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change From Baseline at Week 104 | -0.16 Percent | Standard Error 0.03 |
| Glimepiride | HbA1c Change From Baseline at Week 104 | -0.36 Percent | Standard Error 0.03 |
Comparison: Linagliptin versus Glimepiridep-value: 0.000497.5% CI: [0.09, 0.3]ANCOVA
Primary
HbA1c Change From Baseline at Week 52
This co-primary endpoint, change from baseline, reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications.
Time frame: Baseline and week 52
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change From Baseline at Week 52 | -0.36 Percent | Standard Error 0.03 |
| Glimepiride | HbA1c Change From Baseline at Week 52 | -0.57 Percent | Standard Error 0.03 |
Comparison: Linagliptin versus Glimepiridep-value: 0.000597.5% CI: [0.13, 0.31]ANCOVA
Secondary
2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104
This change from baseline reflects the Week 104 2 hr PPG minus the Baseline 2hr PPG. Means are treatment adjusted for baseline HbA1c, baseline 2hr PPG and number of previous anti-diabetic medications.
Time frame: Baseline and week 104
Population: Patients in the FAS with a valid meal tolerance test (MTT) at baseline and at least one valid on-treatment MTT (MTT104).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | 2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104 | -28.47 mg/dL | Standard Error 4.32 |
| Glimepiride | 2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104 | -18.72 mg/dL | Standard Error 4.28 |
Comparison: Linagliptin versus Glimepiridep-value: 0.091895% CI: [-21.07, 1.59]ANCOVA
Secondary
Body Weight Change From Baseline at Week 104
This key secondary endpoint, change from baseline, reflects the Week 104 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications.
Time frame: Baseline and week 104
Population: This population includes the FAS further restricted to patients with a baseline body weight and one on-treatment body weight measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Body Weight Change From Baseline at Week 104 | -1.39 kg | Standard Error 0.16 |
| Glimepiride | Body Weight Change From Baseline at Week 104 | 1.29 kg | Standard Error 0.16 |
Comparison: Linagliptin versus Glimepiridep-value: <0.000197.5% CI: [-3.17, -2.19]ANCOVA
Secondary
Body Weight Change From Baseline at Week 52
This key secondary endpoint, change from baseline, reflects the Week 52 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications.
Time frame: Baseline and week 52
Population: This population includes the FAS further restricted to patients with a baseline body weight and one on-treatment body weight measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Body Weight Change From Baseline at Week 52 | -1.12 kg | Standard Error 0.13 |
| Glimepiride | Body Weight Change From Baseline at Week 52 | 1.38 kg | Standard Error 0.14 |
Comparison: Linagliptin versus Glimepiridep-value: <0.000197.5% CI: [-2.91, -2.09]ANCOVA
Secondary
Change in Baseline Lipid Parameter Cholesterol at Week 104
Time frame: Baseline and week 104
Population: This population includes the treated set (all patients treated with at least one dose of study drug), and non-missing laboratory data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Change in Baseline Lipid Parameter Cholesterol at Week 104 | 0 mg/dL | Standard Deviation 14 |
| Glimepiride | Change in Baseline Lipid Parameter Cholesterol at Week 104 | 1 mg/dL | Standard Deviation 14 |
Secondary
Change in Baseline Lipid Parameter HDL at Week 104
Time frame: Baseline and week 104
Population: This population includes the treated set (all patients treated with at least one dose of study drug), and non-missing laboratory data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Change in Baseline Lipid Parameter HDL at Week 104 | 1 mg/dl | Standard Deviation 9 |
| Glimepiride | Change in Baseline Lipid Parameter HDL at Week 104 | 0 mg/dl | Standard Deviation 9 |
Secondary
Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104
Time frame: Baseline and week 104
Population: This population includes the treated set (all patients treated with at least one dose of study drug), and non-missing laboratory data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104 | 1 mg/dL | Standard Deviation 23 |
| Glimepiride | Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104 | 3 mg/dL | Standard Deviation 25 |
Secondary
Change in Baseline Lipid Parameter Triglyceride at Week 104
Time frame: Baseline and week 104
Population: This population includes the treated set (all patients treated with at least one dose of study drug), and non-missing laboratory data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Change in Baseline Lipid Parameter Triglyceride at Week 104 | -11 mg/dL | Standard Deviation 153 |
| Glimepiride | Change in Baseline Lipid Parameter Triglyceride at Week 104 | -7 mg/dL | Standard Deviation 148 |
Secondary
Fasting Plasma Glucose (FPG) Change From Baseline at Week 104
This change from baseline reflects the Week 104 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and number of previous anti-diabetic medications.
Time frame: Baseline and week 104
Population: This population includes the FAS further restricted to patients with a baseline FPG and one on-treatment FPG measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Fasting Plasma Glucose (FPG) Change From Baseline at Week 104 | -2.34 mg/dL | Standard Error 1.46 |
| Glimepiride | Fasting Plasma Glucose (FPG) Change From Baseline at Week 104 | -8.72 mg/dL | Standard Error 1.47 |
Comparison: Linagliptin versus Glimepiridep-value: 0.001295% CI: [2.51, 10.25]ANCOVA
Secondary
Fasting Plasma Glucose (FPG) Change From Baseline at Week 52
This change from baseline reflects the Week 52 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and the number of previous anti-diabetic medications.
Time frame: Baseline and week 52
Population: This population includes the FAS further restricted to patients with a baseline FPG and one on-treatment FPG measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | Fasting Plasma Glucose (FPG) Change From Baseline at Week 52 | -8.40 mg/dL | Standard Error 1.25 |
| Glimepiride | Fasting Plasma Glucose (FPG) Change From Baseline at Week 52 | -15.24 mg/dL | Standard Error 1.26 |
Comparison: Linagliptin versus Glimepiridep-value: <0.000195% CI: [3.51, 10.16]ANCOVA
Secondary
HbA1c Change at Week 104
The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement available during the first phase of the study. Last observation carried forward (LOCF) was used as imputation rule.
Time frame: Baseline and week 104
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 104 | -0.21 Percent | Standard Deviation 0.95 |
| Glimepiride | HbA1c Change at Week 104 | -0.41 Percent | Standard Deviation 0.93 |
Secondary
HbA1c Change at Week 12
Time frame: Baseline and week 12
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 12 | -0.43 Percent | Standard Deviation 0.64 |
| Glimepiride | HbA1c Change at Week 12 | -0.75 Percent | Standard Deviation 0.69 |
Secondary
HbA1c Change at Week 16
Time frame: Baseline and week 16
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 16 | -0.45 Percent | Standard Deviation 0.66 |
| Glimepiride | HbA1c Change at Week 16 | -0.78 Percent | Standard Deviation 0.73 |
Secondary
HbA1c Change at Week 28
Time frame: Baseline and week 28
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 28 | -0.43 Percent | Standard Deviation 0.73 |
| Glimepiride | HbA1c Change at Week 28 | -0.74 Percent | Standard Deviation 0.81 |
Secondary
HbA1c Change at Week 4
Difference of base percent value \[Week x(%) - baseline (%)\]
Time frame: Baseline and week 4
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 4 | -0.26 Percent | Standard Deviation 0.41 |
| Glimepiride | HbA1c Change at Week 4 | -0.33 Percent | Standard Deviation 0.46 |
Secondary
HbA1c Change at Week 40
Time frame: Baseline and week 40
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 40 | -0.42 Percent | Standard Deviation 0.77 |
| Glimepiride | HbA1c Change at Week 40 | -0.69 Percent | Standard Deviation 0.83 |
Secondary
HbA1c Change at Week 52
Time frame: Baseline and week 52
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 52 | -0.41 Percent | Standard Deviation 0.82 |
| Glimepiride | HbA1c Change at Week 52 | -0.63 Percent | Standard Deviation 0.85 |
Secondary
HbA1c Change at Week 65
Time frame: Baseline and week 65
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 65 | -0.32 Percent | Standard Deviation 0.91 |
| Glimepiride | HbA1c Change at Week 65 | -0.53 Percent | Standard Deviation 0.87 |
Secondary
HbA1c Change at Week 78
Time frame: Baseline and week 78
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 78 | -0.22 Percent | Standard Deviation 0.92 |
| Glimepiride | HbA1c Change at Week 78 | -0.43 Percent | Standard Deviation 0.9 |
Secondary
HbA1c Change at Week 8
Time frame: Baseline and week 8
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 8 | -0.37 Percent | Standard Deviation 0.59 |
| Glimepiride | HbA1c Change at Week 8 | -0.58 Percent | Standard Deviation 0.62 |
Secondary
HbA1c Change at Week 91
Time frame: Baseline and week 91
Population: The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin | HbA1c Change at Week 91 | -0.21 Percent | Standard Deviation 0.94 |
| Glimepiride | HbA1c Change at Week 91 | -0.43 Percent | Standard Deviation 0.9 |
Secondary
Incidence of Hypoglycaemic Events up to 104 Weeks
A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a HBGM of below 55 mg/dl (3.1 mmol/L)
Time frame: Week 104
Population: The treated set consisted of all patients treated with at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Incidence of Hypoglycaemic Events up to 104 Weeks | 58 Patients |
| Glimepiride | Incidence of Hypoglycaemic Events up to 104 Weeks | 280 Patients |
Comparison: Linagliptin versus Glimepiridep-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Incidence of Hypoglycaemic Events up to 52 Weeks
A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a home blood glucose monitoring (HBGM) of below 55 mg/dl (3.1 mmol/L)
Time frame: Week 52
Population: The treated set consisted of all patients treated with at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Incidence of Hypoglycaemic Events up to 52 Weeks | 41 Patients |
| Glimepiride | Incidence of Hypoglycaemic Events up to 52 Weeks | 249 Patients |
Comparison: Linagliptin versus Glimepiridep-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Patients With HbA1c <6.5% at Week 104
The percentage of patients with an HbA1c value below 6.5% at week 104, based upon patients with baseline HbA1c \>= 6.5%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c \>= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.
Time frame: Week 104
Population: Full analysis set (FAS) patients with non-completers considered as failures (i.e., non-responders) (NCF) and with baseline HbA1c \>=6.5%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Percentage of Patients With HbA1c <6.5% at Week 104 | 10.9 Percentage of patients |
| Glimepiride | Percentage of Patients With HbA1c <6.5% at Week 104 | 14.7 Percentage of patients |
Comparison: Linagliptin versus Glimepiridep-value: 0.02495% CI: [0.498, 0.952]Regression, Logistic
Secondary
Percentage of Patients With HbA1c <6.5% at Week 52
The percentage of patients with an HbA1c value below 6.5% at week 52, based upon patients with baseline HbA1c \>= 6.5%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c \>= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.
Time frame: Week 52
Population: Full analysis set (FAS) patients with non-completers considered as failures (i.e., non-responders) (NCF) and with baseline HbA1c \>=6.5%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Percentage of Patients With HbA1c <6.5% at Week 52 | 16.9 Percentage of patients |
| Glimepiride | Percentage of Patients With HbA1c <6.5% at Week 52 | 22.7 Percentage of patients |
Comparison: Linagliptin versus Glimepiridep-value: 0.002595% CI: [0.489, 0.859]Regression, Logistic
Secondary
Percentage of Patients With HbA1c <7.0% at Week 104
The percentage of patients with an HbA1c value below 7.0% at week 104, based upon patients with baseline HbA1c \>= 7%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c \>= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.
Time frame: Week 104
Population: Full analysis set (FAS) patients with non-completers considered as failures (i.e., non-responders) (NCF) and with baseline HbA1c \>=7.0%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Percentage of Patients With HbA1c <7.0% at Week 104 | 21.0 Percentage of patients |
| Glimepiride | Percentage of Patients With HbA1c <7.0% at Week 104 | 28.3 Percentage of patients |
Comparison: Linagliptin versus Glimepiridep-value: 0.00395% CI: [0.494, 0.866]Regression, Logistic
Secondary
Percentage of Patients With HbA1c <7.0% at Week 52
The percentage of patients with an HbA1c value below 7.0% at week 52, based upon patients with baseline HbA1c \>= 7%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c \>= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.
Time frame: Week 52
Population: Full analysis set (FAS) patients with non-completers considered as failures (i.e., non-responders) (NCF) and with baseline HbA1c \>=7.0%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Percentage of Patients With HbA1c <7.0% at Week 52 | 29.6 Percentage of patients |
| Glimepiride | Percentage of Patients With HbA1c <7.0% at Week 52 | 38.9 Percentage of patients |
Comparison: Linagliptin versus Glimepiridep-value: 0.000495% CI: [0.482, 0.811]Regression, Logistic
Secondary
Percentage of Patients With HbA1c Lowering by 0.5% at Week 104
Occurrence of relative efficacy response, defined as a lowering of 0.5% HbA1c at week 104
Time frame: Week 104
Population: FAS (NCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin | Percentage of Patients With HbA1c Lowering by 0.5% at Week 104 | 26.2 Percentage of patients |
| Glimepiride | Percentage of Patients With HbA1c Lowering by 0.5% at Week 104 | 33.5 Percentage of patients |
Comparison: Linagliptin versus Glimepiridep-value: 0.001895% CI: [0.56, 0.875]Regression, Logistic