ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Empagliflozin (BI 10773) / Linagliptin (BI 1356) Fixed Dose Combination in Treatment naïve and Metformin Treated Type 2 Diabetes Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01422876
Recruitment Status : Completed
First Posted : August 25, 2011
Results First Posted : April 2, 2015
Last Update Posted : April 2, 2015
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: high dose FDC
Drug: BI 10773 high dose
Drug: high dose FDC placebo
Drug: low dose FDC placebo
Drug: high dose BI 10773 placebo
Drug: low dose FDC
Drug: BI 10773 low dose
Drug: linagliptin
Drug: linagliptin placebo
Drug: BI 10773 low dose placebo
Drug: low dose BI 10773 placebo
Enrollment 1405

Recruitment Details  
Pre-assignment Details Of the 1405 patients enrolled and randomized the data for 42 randomized patients were excluded from all analyses due to serious non-compliance. Therefore, 1363 patients were included in the analyses.
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg
Hide Arm/Group Description Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Period Title: Week 24
Started 137 136 141 140 132 137 136 135 134 135
Completed 131 133 136 132 125 131 130 128 128 125
Not Completed 6 3 5 8 7 6 6 7 6 10
Reason Not Completed
Lost to Follow-up             1             1             2             4             2             0             1             3             3             4
Consent withdrawn             5             1             3             4             5             6             5             4             3             6
Death             0             1             0             0             0             0             0             0             0             0
Period Title: Week 52
Started 137 136 141 140 132 137 136 135 134 135
Completed 125 126 128 122 117 120 120 112 113 118
Not Completed 12 10 13 18 15 17 16 23 21 17
Reason Not Completed
Lost to Follow-up             3             5             7             5             8             5             5             8             7             8
Consent withdrawn             9             4             6             12             7             12             10             12             13             9
Death             0             1             0             1             0             0             1             3             1             0
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg Total
Hide Arm/Group Description

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Total of all reporting groups
Overall Number of Baseline Participants 134 135 140 137 128 134 135 133 132 133 1341
Hide Baseline Analysis Population Description
FAS
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 134 participants 135 participants 140 participants 137 participants 128 participants 134 participants 135 participants 133 participants 132 participants 133 participants 1341 participants
57.1  (10.2) 56.2  (10.3) 55.5  (10.0) 56.1  (10.5) 56.2  (10.0) 54.2  (10.0) 55.2  (9.8) 56.0  (9.3) 53.9  (10.5) 53.8  (11.5) 55.4  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 135 participants 140 participants 137 participants 128 participants 134 participants 135 participants 133 participants 132 participants 133 participants 1341 participants
Female
62
  46.3%
52
  38.5%
75
  53.6%
59
  43.1%
64
  50.0%
64
  47.8%
62
  45.9%
56
  42.1%
68
  51.5%
58
  43.6%
620
  46.2%
Male
72
  53.7%
83
  61.5%
65
  46.4%
78
  56.9%
64
  50.0%
70
  52.2%
73
  54.1%
77
  57.9%
64
  48.5%
75
  56.4%
721
  53.8%
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients
Hide Description Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.
Time Frame Baseline and 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg
Hide Arm/Group Description:

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 134 135 140 137 128
Least Squares Mean (Standard Error)
Unit of Measure: % change from baseline
-1.19  (0.06) -1.08  (0.06) -0.62  (0.06) -0.66  (0.06) -0.70  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p<0.0001), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.75 to -0.41
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p<0.0001), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.67 to -0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p<0.0001), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.59 to -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p<0.0001), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.56 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients
Hide Description Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.
Time Frame Baseline and 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised to and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg
Hide Arm/Group Description:

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 134 135 133 132 133
Least Squares Mean (Standard Error)
Unit of Measure: % change from baseline
-1.08  (0.07) -1.24  (0.07) -0.95  (0.07) -0.83  (0.07) -0.67  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1785
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.33 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.61 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.61 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.76 to -0.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients
Hide Description Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients.
Time Frame Baseline and 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg
Hide Arm/Group Description:

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Ora

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 133 134 139 136 127
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL change from baseline
-35.25  (2.53) -32.18  (2.52) -18.83  (2.47) -20.84  (2.50) -13.05  (2.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -16.43
Confidence Interval (2-Sided) 95%
-23.37 to -9.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.54
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -22.20
Confidence Interval (2-Sided) 95%
-29.30 to -15.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.62
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -11.34
Confidence Interval (2-Sided) 95%
-18.31 to -4.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.55
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -19.12
Confidence Interval (2-Sided) 95%
-26.21 to -12.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.61
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients
Hide Description Change from baseline in fasting plasma glucose at week 24 for Treatment Naive patients.
Time Frame Baseline and 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg
Hide Arm/Group Description:

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 134 135 133 132 133
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL change from baseline
-29.55  (2.67) -28.21  (2.66) -24.24  (2.68) -22.39  (2.69) -5.92  (2.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1605
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.31
Confidence Interval (2-Sided) 95%
-12.74 to 2.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1246
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.82
Confidence Interval (2-Sided) 95%
-13.25 to 1.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.78
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -23.63
Confidence Interval (2-Sided) 95%
-31.06 to -16.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.78
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline fasting plasma glucose (p<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -22.29
Confidence Interval (2-Sided) 95%
-29.71 to -14.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.77
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Body Weight for Metformin Background Patients
Hide Description Change from baseline in body weight for Metformin Background patients.
Time Frame Baseline and 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg
Hide Arm/Group Description:

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 134 135 140 137 128
Least Squares Mean (Standard Error)
Unit of Measure: kg change from baseline
-2.99  (0.31) -2.60  (0.30) -3.18  (0.30) -2.53  (0.30) -0.69  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6604
Comments Not an alpha protected test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.65 to 1.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.30
Confidence Interval (2-Sided) 95%
-3.15 to -1.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.44
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8757
Comments Not an alpha protected test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.91 to 0.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p<0.0001) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.91
Confidence Interval (2-Sided) 95%
-2.77 to -1.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.44
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Body Weight for Treatment Naive Patients
Hide Description Change from baseline in body weight for Treatment Naive patients.
Time Frame Baseline and 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
Arm/Group Title Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg
Hide Arm/Group Description:

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 134 135 133 132 133
Least Squares Mean (Standard Error)
Unit of Measure: kg change from baseline
-2.00  (0.36) -2.74  (0.36) -2.13  (0.36) -2.27  (0.37) -0.78  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 25 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8010
Comments Not an alpha protected test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.88 to 1.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 10 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3616
Comments Not an alpha protected test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-1.48 to 0.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0178
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-2.23 to -0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Model for Week 24 includes baseline weight (p<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.96
Confidence Interval (2-Sided) 95%
-2.97 to -0.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Occurrence of Treat to Target Efficacy Response for Metformin Background Patients
Hide Description Occurrence of the treat-to-target efficacy response for Metformin Background patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline.
Time Frame 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS- Metformin background patients randomised and treated who had a baseline (HbA1c>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.
Arm/Group Title Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Metformin Background: Empagliflozin 25 mg Metformin Background: Empagliflozin 10 mg Metformin Background: Linagliptin 5 mg
Hide Arm/Group Description:

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 123 128 132 125 119
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % of patients satisfying HbA1c <7.0%
61.8
(52.6 to 70.4)
57.8
(48.8 to 66.5)
32.6
(24.7 to 41.3)
28.0
(20.3 to 36.7)
36.1
(27.5 to 45.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 25 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.191
Confidence Interval (2-Sided) 95%
2.319 to 7.573
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Empagliflozin 10 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.500
Confidence Interval (2-Sided) 95%
2.474 to 8.184
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.495
Confidence Interval (2-Sided) 95%
1.920 to 6.363
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg, Metformin Background: Linagliptin 5 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.795
Confidence Interval (2-Sided) 95%
1.562 to 5.001
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients
Hide Description Occurrence of the treat-to-target efficacy response for Treatment Naive patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline.
Time Frame 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS-treatment naive patients randomised and treated who had a baseline (HbA1c>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.
Arm/Group Title Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Treatment Naive: Empagliflozin 25 mg Treatment Naive: Empagliflozin 10 mg Treatment Naive: Linagliptin 5 mg
Hide Arm/Group Description:

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Overall Number of Participants Analyzed 121 122 118 121 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % of patients satisfying HbA1c <7.0%
55.4
(46.1 to 64.4)
62.3
(53.1 to 70.9)
41.5
(32.5 to 51.0)
38.8
(30.1 to 48.1)
32.3
(24.3 to 41.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 25 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0224
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.893
Confidence Interval (2-Sided) 95%
1.095 to 3.274
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Empagliflozin 10 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.961
Confidence Interval (2-Sided) 95%
1.697 to 5.169
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.065
Confidence Interval (2-Sided) 95%
1.768 to 5.314
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg, Treatment Naive: Linagliptin 5 mg
Comments Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.303
Confidence Interval (2-Sided) 95%
2.462 to 7.522
Estimation Comments [Not Specified]
Time Frame From first trial medication intake until 7 days after last drug intake during the 52-week study period
Adverse Event Reporting Description One patient was randomized to treatment with Empa/Lina 25/5 but was treated with Empa 10 from the start of trial for 6 weeks. For efficacy, the patient was analyzed as randomized (Empa/Lina 25/5) and for safety the patient was analyzed as first medication taken (Empa 10).
 
Arm/Group Title Empagliflozin 25 mg/Linagliptin 5 mg Empagliflozin 10 mg/Linagliptin 5 mg Empagliflozin 25 mg Empagliflozin 10 mg Linagliptin 5 mg
Hide Arm/Group Description Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral
All-Cause Mortality
Empagliflozin 25 mg/Linagliptin 5 mg Empagliflozin 10 mg/Linagliptin 5 mg Empagliflozin 25 mg Empagliflozin 10 mg Linagliptin 5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empagliflozin 25 mg/Linagliptin 5 mg Empagliflozin 10 mg/Linagliptin 5 mg Empagliflozin 25 mg Empagliflozin 10 mg Linagliptin 5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/273 (4.40%)   16/272 (5.88%)   19/276 (6.88%)   16/275 (5.82%)   10/267 (3.75%) 
Cardiac disorders           
Acute coronary syndrome  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Angina pectoris  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Angina unstable  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Coronary artery disease  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Coronary artery occlusion  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Hypertensive heart disease  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Myocardial infarction  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  1/267 (0.37%) 
Palpitations  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Silent myocardial infarction  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Gastrointestinal disorders           
Abdominal adhesions  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Abdominal pain  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Abdominal strangulated hernia  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Colitis ischaemic  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Intestinal perforation  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Mechanical ileus  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Pancreatitis chronic  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
General disorders           
Chest pain  1  0/273 (0.00%)  2/272 (0.74%)  1/276 (0.36%)  1/275 (0.36%)  0/267 (0.00%) 
Non-cardiac chest pain  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/273 (0.00%)  0/272 (0.00%)  2/276 (0.72%)  0/275 (0.00%)  0/267 (0.00%) 
Cholecystitis acute  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  1/267 (0.37%) 
Hepatic mass  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Infections and infestations           
Bacterial infection  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Cellulitis  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Cystitis  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Diverticulitis  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Encephalitis viral  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Meningitis tuberculous  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Peritonitis  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Pneumonia viral  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Pyelonephritis acute  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Pyelonephritis chronic  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Tooth abscess  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Urinary tract infection  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Urosepsis  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Injury, poisoning and procedural complications           
Chemical injury  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Fibula fracture  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Joint dislocation  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Lower limb fracture  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Rib fracture  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Road traffic accident  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Seroma  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Tendon rupture  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Investigations           
Troponin increased  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Metabolism and nutrition disorders           
Alkalosis  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Dehydration  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  1/267 (0.37%) 
Hyperglycaemia  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Hypokalaemia  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Musculoskeletal and connective tissue disorders           
Flank pain  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Myofascial pain syndrome  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Osteoarthritis  1  0/273 (0.00%)  1/272 (0.37%)  1/276 (0.36%)  1/275 (0.36%)  0/267 (0.00%) 
Rotator cuff syndrome  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Adenoid cystic carcinoma  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Basal cell carcinoma  1  1/273 (0.37%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Breast cancer  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Clear cell renal cell carcinoma  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Gastrointestinal carcinoma  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Lung adenocarcinoma  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Lung neoplasm  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Metastases to peritoneum  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Non-small cell lung cancer metastatic  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Ovarian cancer  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Parathyroid tumour benign  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  1/267 (0.37%) 
Prostate cancer  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Renal cancer  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Squamous cell carcinoma  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Uterine leiomyoma  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Nervous system disorders           
Transient ischaemic attack  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  2/275 (0.73%)  0/267 (0.00%) 
Brain oedema  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Cerebral infarction  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Cerebrovascular accident  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Dementia Alzheimer's type  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Encephalopathy  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Haemorrhagic stroke  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Lethargy  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Syncope  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Psychiatric disorders           
Confusional state  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Mental status changes  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Renal and urinary disorders           
Calculus bladder  1  1/273 (0.37%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  0/267 (0.00%) 
Calculus ureteric  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  1/275 (0.36%)  0/267 (0.00%) 
Hydronephrosis  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Renal colic  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Renal failure acute  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Reproductive system and breast disorders           
Ovarian cyst  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Postmenopausal haemorrhage  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Rectocele  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Pulmonary embolism  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Skin and subcutaneous tissue disorders           
Diabetic foot  1  0/273 (0.00%)  0/272 (0.00%)  0/276 (0.00%)  1/275 (0.36%)  0/267 (0.00%) 
Surgical and medical procedures           
Finger amputation  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Vascular disorders           
Hypotension  1  0/273 (0.00%)  1/272 (0.37%)  0/276 (0.00%)  0/275 (0.00%)  1/267 (0.37%) 
Varicose vein  1  0/273 (0.00%)  0/272 (0.00%)  1/276 (0.36%)  0/275 (0.00%)  0/267 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empagliflozin 25 mg/Linagliptin 5 mg Empagliflozin 10 mg/Linagliptin 5 mg Empagliflozin 25 mg Empagliflozin 10 mg Linagliptin 5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   80/273 (29.30%)   86/272 (31.62%)   70/276 (25.36%)   83/275 (30.18%)   94/267 (35.21%) 
Infections and infestations           
Urinary tract infection  1  27/273 (9.89%)  29/272 (10.66%)  25/276 (9.06%)  30/275 (10.91%)  27/267 (10.11%) 
Nasopharyngitis  1  18/273 (6.59%)  16/272 (5.88%)  10/276 (3.62%)  16/275 (5.82%)  20/267 (7.49%) 
Upper respiratory tract infection  1  19/273 (6.96%)  19/272 (6.99%)  18/276 (6.52%)  13/275 (4.73%)  16/267 (5.99%) 
Metabolism and nutrition disorders           
Hyperglycaemia  1  8/273 (2.93%)  8/272 (2.94%)  12/276 (4.35%)  12/275 (4.36%)  24/267 (8.99%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  5/273 (1.83%)  14/272 (5.15%)  13/276 (4.71%)  10/275 (3.64%)  12/267 (4.49%) 
Nervous system disorders           
Headache  1  16/273 (5.86%)  15/272 (5.51%)  13/276 (4.71%)  19/275 (6.91%)  24/267 (8.99%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01422876     History of Changes
Other Study ID Numbers: 1275.1
2011-000383-10 ( EudraCT Number: EudraCT )
First Submitted: August 23, 2011
First Posted: August 25, 2011
Results First Submitted: January 15, 2015
Results First Posted: April 2, 2015
Last Update Posted: April 2, 2015