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Efficacy and Safety of Empagliflozin (BI 10773) With Metformin in Patients With Type 2 Diabetes

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: NCT01167881
Recruitment Status : Completed
First Posted : July 22, 2010
Results First Posted : August 8, 2014
Last Update Posted : September 2, 2016
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: BI 10773
Drug: Glimepiride
Drug: Placebo
Enrollment 1549
Recruitment Details  
Pre-assignment Details An optional 2-year extension was implemented in this trial through a protocol amendment, which brought the total length of treatment to 4 years. However, some sites did not participate in the 2-year extension, and so considered patients to have completed treatment after 2 years.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Period Title: Overall Study
Started 769 780
Completed After 2 Years Treatment 95 127
Completed After 4 Years Treatment 515 462
Completed 610 589
Not Completed 159 191
Reason Not Completed
Adverse Event             47             51
Lack of Efficacy             4             7
Non compliant with protocol             9             18
Lost to Follow-up             19             20
Patient refusal to cont., not due to AE             45             40
Not treated             4             0
Other not defined above             31             55
Arm/Group Title Empaglifozin 25 mg Glimepiride Total
Hide Arm/Group Description

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Total of all reporting groups
Overall Number of Baseline Participants 765 780 1545
Hide Baseline Analysis Population Description
Full Analysis Set (FAS), All patients randomised, treated with at least one dose of study drug, and with a baseline HbA1c value.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 765 participants 780 participants 1545 participants
56.2  (10.3) 55.7  (10.4) 55.9  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 765 participants 780 participants 1545 participants
Female
333
  43.5%
359
  46.0%
692
  44.8%
Male
432
  56.5%
421
  54.0%
853
  55.2%
1.Primary Outcome
Title The Change From Baseline in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame Baseline and 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

FAS (LOCF) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.66  (0.03) -0.55  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was tested through a two-sided 97.5% confidence interval for the treatment effect of empagliflozin minus the effect of glimepiride in change from baseline in HbA1c. The null-hypothesis of material inferiority of empagliflozin was rejected if the confidence interval is entirely below the non-inferiority margin 0.3%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline HbA1c as linear covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.11
Confidence Interval (2-Sided) 97.5%
-0.20 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0153
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline HbA1c as linear covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.11
Confidence Interval (2-Sided) 97.5%
-0.20 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.04
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Change in Body Weight From Baseline After 104 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: kilograms
-3.11  (0.13) 1.33  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline weight, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.46
Confidence Interval (2-Sided) 97.5%
-4.87 to -4.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Occurrence of Confirmed Hypoglycaemic Events During 104 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set, all patients treated with at least one dose of randomised study drug.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Measure Type: Number
Unit of Measure: participants
19 189
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusting for baseline HbA1c (<8.5 / >=8.5).
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.102
Confidence Interval (2-Sided) 97.5%
0.060 to 0.173
Estimation Comments [Not Specified]
4.Secondary Outcome
Title The Change in Systolic Blood Pressure (SBP) From Baseline After 104 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

FAS (LOCF-H) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: mmHg
-3.1  (0.5) 2.5  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline SBP, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.6
Confidence Interval (2-Sided) 97.5%
-7.0 to -4.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.6
Estimation Comments [Not Specified]
5.Secondary Outcome
Title The Change in Diastolic Blood Pressure (DBP) From Baseline After 104 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF-H) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: mmHg
-1.8  (0.3) 0.9  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for main analysis (104 weeks):

  1. Non-inferiority in HbA1c change from baseline at 104 weeks,
  2. Superiority in body weight change from baseline at 104 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 104 weeks,
  4. Superiority in HbA1c change from baseline at 104 weeks,
  5. Superiority in systolic blood pressure change from baseline at 104 weeks,
  6. Superiority in diastolic blood pressure change from baseline at 104 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline DBP, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.7
Confidence Interval (2-Sided) 97.5%
-3.5 to -1.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title The Change From Baseline in HbA1c After 52 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.73  (0.03) -0.66  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for first interim analysis (52 weeks):

  1. Non-inferiority in HbA1c change from baseline at 52 weeks,
  2. Superiority in body weight change from baseline at 52 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 52 weeks,
  4. Superiority in systolic blood pressure change from baseline at 52 weeks,
  5. Superiority in diastolic blood pressure change from baseline at 52 weeks.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was tested through a two-sided 97.5% confidence interval for the treatment effect of empagliflozin minus the effect of glimepiride in change from baseline in HbA1c. The null-hypothesis of material inferiority of empagliflozin was rejected if the confidence interval is entirely below the non-inferiority margin 0.3%.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline HbA1c as linear covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.07
Confidence Interval (2-Sided) 97.5%
-0.16 to 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.04
Estimation Comments [Not Specified]
7.Secondary Outcome
Title The Change in Body Weight From Baseline After 52 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: kilograms
-3.21  (0.12) 1.59  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for first interim analysis (52 weeks):

  1. Non-inferiority in HbA1c change from baseline at 52 weeks,
  2. Superiority in body weight change from baseline at 52 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 52 weeks,
  4. Superiority in systolic blood pressure change from baseline at 52 weeks,
  5. Superiority in diastolic blood pressure change from baseline at 52 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline weight, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.81
Confidence Interval (2-Sided) 97.5%
-5.16 to -4.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.16
Estimation Comments [Not Specified]
8.Secondary Outcome
Title The Occurrence of Confirmed Hypoglycaemic Events During 52 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set, all patients treated with at least one dose of randomised study drug.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Measure Type: Number
Unit of Measure: participants
12 159
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for first interim analysis (52 weeks):

  1. Non-inferiority in HbA1c change from baseline at 52 weeks,
  2. Superiority in body weight change from baseline at 52 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 52 weeks,
  4. Superiority in systolic blood pressure change from baseline at 52 weeks,
  5. Superiority in diastolic blood pressure change from baseline at 52 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusting for baseline HbA1c (<8.5 / >=8.5).
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.077
Confidence Interval (2-Sided) 97.5%
0.040 to 0.148
Estimation Comments [Not Specified]
9.Secondary Outcome
Title The Change in Systolic Blood Pressure (SBP) From Baseline After 52 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF-H) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: mmHg
-3.6  (0.5) 2.2  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for first interim analysis (52 weeks):

  1. Non-inferiority in HbA1c change from baseline at 52 weeks,
  2. Superiority in body weight change from baseline at 52 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 52 weeks,
  4. Superiority in systolic blood pressure change from baseline at 52 weeks,
  5. Superiority in diastolic blood pressure change from baseline at 52 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline SBP, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.8
Confidence Interval (2-Sided) 97.5%
-7.3 to -4.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title The Change in Diastolic Blood Pressure (DBP) From Baseline After 52 Weeks of Treatment.
Hide Description [Not Specified]
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (LOCF-H) – Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF); Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.
Arm/Group Title Empaglifozin 25 mg Glimepiride
Hide Arm/Group Description:

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Overall Number of Participants Analyzed 765 780
Mean (Standard Error)
Unit of Measure: mmHg
-1.9  (0.3) 1.0  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empaglifozin 25 mg, Glimepiride
Comments

Testing Hierarchy for first interim analysis (52 weeks):

  1. Non-inferiority in HbA1c change from baseline at 52 weeks,
  2. Superiority in body weight change from baseline at 52 weeks,
  3. Superiority in occurrence of confirmed hypoglycaemic adverse events at 52 weeks,
  4. Superiority in systolic blood pressure change from baseline at 52 weeks,
  5. Superiority in diastolic blood pressure change from baseline at 52 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The superiority tests performed at 104 weeks and the superiority tests performed at 52 weeks both used a nominal significance level of 2.5% to maintain the overall significance level of 5%.
Method ANCOVA
Comments ANCOVA with treatment, geographical region, renal function at baseline as fixed effects and baseline DBP, baseline HbA1c as linear covariates.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.8
Confidence Interval (2-Sided) 97.5%
-3.7 to -2.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4
Estimation Comments [Not Specified]
Time Frame Up to 4 years.
Adverse Event Reporting Description All adverse events (AE), serious and non-serious, occurring during the course of the clinical trial were collected, documented, and reported to the sponsor by the investigator on the appropriate case report form (CRF) or serious adverse event (SAE) reporting forms.
 
Arm/Group Title Empa 25mg Glimepiride
Hide Arm/Group Description Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily. Empagliflozin: 25 mg once daily Placebo: Placebo matching Glimepiride Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily. Glimepiride: 1-4 mg once daily Placebo: Placebo matching Empagliflozin
All-Cause Mortality
Empa 25mg Glimepiride
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa 25mg Glimepiride
Affected / at Risk (%) Affected / at Risk (%)
Total   161/765 (21.05%)   153/780 (19.62%) 
Blood and lymphatic system disorders     
Anaemia  1  1/765 (0.13%)  2/780 (0.26%) 
Iron deficiency anaemia  1  1/765 (0.13%)  0/780 (0.00%) 
Thrombocytopenia  1  1/765 (0.13%)  0/780 (0.00%) 
Cardiac disorders     
Coronary artery disease  1  3/765 (0.39%)  8/780 (1.03%) 
Acute myocardial infarction  1  1/765 (0.13%)  7/780 (0.90%) 
Angina unstable  1  4/765 (0.52%)  4/780 (0.51%) 
Atrial fibrillation  1  4/765 (0.52%)  2/780 (0.26%) 
Myocardial infarction  1  0/765 (0.00%)  3/780 (0.38%) 
Myocardial ischaemia  1  1/765 (0.13%)  3/780 (0.38%) 
Angina pectoris  1  1/765 (0.13%)  2/780 (0.26%) 
Cardiac failure  1  2/765 (0.26%)  1/780 (0.13%) 
Cardiac failure congestive  1  0/765 (0.00%)  2/780 (0.26%) 
Palpitations  1  2/765 (0.26%)  0/780 (0.00%) 
Acute coronary syndrome  1  1/765 (0.13%)  0/780 (0.00%) 
Arrhythmia  1  1/765 (0.13%)  0/780 (0.00%) 
Arteriosclerosis coronary artery  1  1/765 (0.13%)  0/780 (0.00%) 
Cardiac disorder  1  0/765 (0.00%)  1/780 (0.13%) 
Cardiac tamponade  1  0/765 (0.00%)  1/780 (0.13%) 
Tachycardia  1  1/765 (0.13%)  0/780 (0.00%) 
Ventricle rupture  1  0/765 (0.00%)  1/780 (0.13%) 
Ventricular tachycardia  1  1/765 (0.13%)  0/780 (0.00%) 
Congenital, familial and genetic disorders     
Phimosis  1  2/765 (0.26%)  0/780 (0.00%) 
Ear and labyrinth disorders     
Otosclerosis  1  0/765 (0.00%)  1/780 (0.13%) 
Tinnitus  1  0/765 (0.00%)  1/780 (0.13%) 
Vertigo  1  0/765 (0.00%)  1/780 (0.13%) 
Endocrine disorders     
Goitre  1  1/765 (0.13%)  1/780 (0.13%) 
Pituitary-dependent Cushing's syndrome  1  0/765 (0.00%)  1/780 (0.13%) 
Eye disorders     
Retinal detachment  1  1/765 (0.13%)  3/780 (0.38%) 
Cataract  1  0/765 (0.00%)  2/780 (0.26%) 
Diabetic retinopathy  1  1/765 (0.13%)  0/780 (0.00%) 
Endocrine ophthalmopathy  1  0/765 (0.00%)  1/780 (0.13%) 
Open angle glaucoma  1  0/765 (0.00%)  1/780 (0.13%) 
Retinal neovascularisation  1  0/765 (0.00%)  1/780 (0.13%) 
Vitreous haemorrhage  1  1/765 (0.13%)  0/780 (0.00%) 
Gastrointestinal disorders     
Inguinal hernia  1  4/765 (0.52%)  0/780 (0.00%) 
Gastrointestinal haemorrhage  1  3/765 (0.39%)  0/780 (0.00%) 
Abdominal pain  1  2/765 (0.26%)  2/780 (0.26%) 
Abdominal pain upper  1  2/765 (0.26%)  0/780 (0.00%) 
Dyspepsia  1  0/765 (0.00%)  2/780 (0.26%) 
Pancreatitis acute  1  0/765 (0.00%)  2/780 (0.26%) 
Umbilical hernia  1  2/765 (0.26%)  1/780 (0.13%) 
Vomiting  1  2/765 (0.26%)  0/780 (0.00%) 
Abdominal hernia  1  1/765 (0.13%)  1/780 (0.13%) 
Anorectal varices  1  0/765 (0.00%)  1/780 (0.13%) 
Anorectal varices haemorrhage  1  0/765 (0.00%)  1/780 (0.13%) 
Colitis  1  1/765 (0.13%)  0/780 (0.00%) 
Crohn's disease  1  0/765 (0.00%)  1/780 (0.13%) 
Diverticulum intestinal  1  0/765 (0.00%)  1/780 (0.13%) 
Enterocolitis haemorrhagic  1  1/765 (0.13%)  0/780 (0.00%) 
Gastric ulcer  1  0/765 (0.00%)  1/780 (0.13%) 
Gastritis  1  0/765 (0.00%)  1/780 (0.13%) 
Haemorrhoids  1  1/765 (0.13%)  1/780 (0.13%) 
Hiatus hernia  1  1/765 (0.13%)  1/780 (0.13%) 
Impaired gastric emptying  1  0/765 (0.00%)  1/780 (0.13%) 
Incarcerated inguinal hernia  1  0/765 (0.00%)  1/780 (0.13%) 
Intestinal obstruction  1  1/765 (0.13%)  0/780 (0.00%) 
Large intestine polyp  1  1/765 (0.13%)  0/780 (0.00%) 
Oesophageal varices haemorrhage  1  0/765 (0.00%)  1/780 (0.13%) 
Pancreatitis  1  1/765 (0.13%)  0/780 (0.00%) 
Proctitis haemorrhagic  1  1/765 (0.13%)  0/780 (0.00%) 
Rectal haemorrhage  1  1/765 (0.13%)  0/780 (0.00%) 
Rectal polyp  1  0/765 (0.00%)  1/780 (0.13%) 
Volvulus  1  1/765 (0.13%)  0/780 (0.00%) 
General disorders     
Chest pain  1  1/765 (0.13%)  5/780 (0.64%) 
Non-cardiac chest pain  1  1/765 (0.13%)  2/780 (0.26%) 
Cyst  1  0/765 (0.00%)  1/780 (0.13%) 
Hernia  1  1/765 (0.13%)  0/780 (0.00%) 
Multi-organ failure  1  1/765 (0.13%)  0/780 (0.00%) 
Pain  1  1/765 (0.13%)  0/780 (0.00%) 
Pyrexia  1  1/765 (0.13%)  1/780 (0.13%) 
Sudden death  1  1/765 (0.13%)  0/780 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  4/765 (0.52%)  5/780 (0.64%) 
Cholecystitis acute  1  1/765 (0.13%)  2/780 (0.26%) 
Cholangitis  1  0/765 (0.00%)  1/780 (0.13%) 
Cholangitis acute  1  0/765 (0.00%)  1/780 (0.13%) 
Cholecystitis  1  1/765 (0.13%)  1/780 (0.13%) 
Cholecystitis chronic  1  1/765 (0.13%)  0/780 (0.00%) 
Drug-induced liver injury  1  0/765 (0.00%)  1/780 (0.13%) 
Hepatic cirrhosis  1  1/765 (0.13%)  1/780 (0.13%) 
Hepatic failure  1  1/765 (0.13%)  0/780 (0.00%) 
Hepatitis acute  1  0/765 (0.00%)  1/780 (0.13%) 
Liver disorder  1  0/765 (0.00%)  1/780 (0.13%) 
Non-alcoholic steatohepatitis  1  0/765 (0.00%)  1/780 (0.13%) 
Portal hypertension  1  0/765 (0.00%)  1/780 (0.13%) 
Immune system disorders     
Drug hypersensitivity  1  0/765 (0.00%)  3/780 (0.38%) 
Infections and infestations     
Gastroenteritis  1  4/765 (0.52%)  0/780 (0.00%) 
Cellulitis  1  3/765 (0.39%)  0/780 (0.00%) 
Diverticulitis  1  3/765 (0.39%)  0/780 (0.00%) 
Viral infection  1  3/765 (0.39%)  0/780 (0.00%) 
Bronchitis  1  0/765 (0.00%)  2/780 (0.26%) 
Erysipelas  1  1/765 (0.13%)  2/780 (0.26%) 
Post procedural infection  1  0/765 (0.00%)  2/780 (0.26%) 
Sepsis  1  1/765 (0.13%)  2/780 (0.26%) 
Abscess limb  1  1/765 (0.13%)  1/780 (0.13%) 
Appendicitis  1  1/765 (0.13%)  1/780 (0.13%) 
Bacteraemia  1  0/765 (0.00%)  1/780 (0.13%) 
Cystitis  1  1/765 (0.13%)  0/780 (0.00%) 
Cystitis escherichia  1  1/765 (0.13%)  0/780 (0.00%) 
Dengue fever  1  0/765 (0.00%)  1/780 (0.13%) 
Diarrhoea infectious  1  1/765 (0.13%)  1/780 (0.13%) 
Escherichia bacteraemia  1  1/765 (0.13%)  0/780 (0.00%) 
Febrile infection  1  0/765 (0.00%)  1/780 (0.13%) 
Gastroenteritis salmonella  1  0/765 (0.00%)  1/780 (0.13%) 
Hepatitis E  1  1/765 (0.13%)  0/780 (0.00%) 
Infectious mononucleosis  1  1/765 (0.13%)  0/780 (0.00%) 
Kidney infection  1  1/765 (0.13%)  0/780 (0.00%) 
Liver abscess  1  0/765 (0.00%)  1/780 (0.13%) 
Lobar pneumonia  1  0/765 (0.00%)  1/780 (0.13%) 
Localised infection  1  0/765 (0.00%)  1/780 (0.13%) 
Lower respiratory tract infection  1  0/765 (0.00%)  1/780 (0.13%) 
Lung infection  1  1/765 (0.13%)  0/780 (0.00%) 
Nasopharyngitis  1  0/765 (0.00%)  1/780 (0.13%) 
Osteomyelitis  1  0/765 (0.00%)  1/780 (0.13%) 
Pelvic abscess  1  1/765 (0.13%)  0/780 (0.00%) 
Peritonitis bacterial  1  0/765 (0.00%)  1/780 (0.13%) 
Pneumonia bacterial  1  1/765 (0.13%)  0/780 (0.00%) 
Pneumonia legionella  1  0/765 (0.00%)  1/780 (0.13%) 
Pyelonephritis  1  0/765 (0.00%)  1/780 (0.13%) 
Pyelonephritis acute  1  1/765 (0.13%)  1/780 (0.13%) 
Salmonellosis  1  1/765 (0.13%)  0/780 (0.00%) 
Septic shock  1  1/765 (0.13%)  0/780 (0.00%) 
Sialoadenitis  1  1/765 (0.13%)  0/780 (0.00%) 
Tuberculosis gastrointestinal  1  1/765 (0.13%)  0/780 (0.00%) 
Upper respiratory tract infection  1  0/765 (0.00%)  1/780 (0.13%) 
Urosepsis  1  0/765 (0.00%)  1/780 (0.13%) 
Injury, poisoning and procedural complications     
Fall  1  8/765 (1.05%)  1/780 (0.13%) 
Ankle fracture  1  3/765 (0.39%)  1/780 (0.13%) 
Fibula fracture  1  2/765 (0.26%)  0/780 (0.00%) 
Humerus fracture  1  2/765 (0.26%)  1/780 (0.13%) 
Incisional hernia  1  0/765 (0.00%)  2/780 (0.26%) 
Meniscus injury  1  1/765 (0.13%)  2/780 (0.26%) 
Road traffic accident  1  0/765 (0.00%)  2/780 (0.26%) 
Subdural haematoma  1  0/765 (0.00%)  2/780 (0.26%) 
Tibia fracture  1  2/765 (0.26%)  0/780 (0.00%) 
Traumatic fracture  1  2/765 (0.26%)  1/780 (0.13%) 
Burns third degree  1  1/765 (0.13%)  0/780 (0.00%) 
Comminuted fracture  1  1/765 (0.13%)  0/780 (0.00%) 
Femur fracture  1  1/765 (0.13%)  0/780 (0.00%) 
Foreign body  1  0/765 (0.00%)  1/780 (0.13%) 
Head injury  1  0/765 (0.00%)  1/780 (0.13%) 
Jaw fracture  1  0/765 (0.00%)  1/780 (0.13%) 
Joint dislocation  1  0/765 (0.00%)  1/780 (0.13%) 
Laceration  1  0/765 (0.00%)  1/780 (0.13%) 
Ligament sprain  1  1/765 (0.13%)  0/780 (0.00%) 
Limb injury  1  1/765 (0.13%)  0/780 (0.00%) 
Muscle rupture  1  0/765 (0.00%)  1/780 (0.13%) 
Overdose  1  0/765 (0.00%)  1/780 (0.13%) 
Post procedural constipation  1  1/765 (0.13%)  0/780 (0.00%) 
Post procedural haemorrhage  1  1/765 (0.13%)  0/780 (0.00%) 
Procedural headache  1  1/765 (0.13%)  0/780 (0.00%) 
Radius fracture  1  1/765 (0.13%)  0/780 (0.00%) 
Soft tissue injury  1  1/765 (0.13%)  0/780 (0.00%) 
Tendon rupture  1  0/765 (0.00%)  1/780 (0.13%) 
Investigations     
Liver function test abnormal  1  1/765 (0.13%)  0/780 (0.00%) 
Metabolism and nutrition disorders     
Obesity  1  0/765 (0.00%)  2/780 (0.26%) 
Dehydration  1  0/765 (0.00%)  1/780 (0.13%) 
Diabetes mellitus inadequate control  1  0/765 (0.00%)  1/780 (0.13%) 
Electrolyte imbalance  1  1/765 (0.13%)  0/780 (0.00%) 
Fluid overload  1  0/765 (0.00%)  1/780 (0.13%) 
Gout  1  1/765 (0.13%)  0/780 (0.00%) 
Hyperglycaemia  1  0/765 (0.00%)  1/780 (0.13%) 
Hyperkalaemia  1  0/765 (0.00%)  1/780 (0.13%) 
Hypoglycaemia  1  0/765 (0.00%)  1/780 (0.13%) 
Hypokalaemia  1  1/765 (0.13%)  0/780 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  4/765 (0.52%)  4/780 (0.51%) 
Back pain  1  2/765 (0.26%)  1/780 (0.13%) 
Foot deformity  1  2/765 (0.26%)  0/780 (0.00%) 
Intervertebral disc protrusion  1  0/765 (0.00%)  2/780 (0.26%) 
Spinal osteoarthritis  1  2/765 (0.26%)  2/780 (0.26%) 
Arthralgia  1  1/765 (0.13%)  1/780 (0.13%) 
Arthritis  1  0/765 (0.00%)  1/780 (0.13%) 
Cervical spinal stenosis  1  1/765 (0.13%)  0/780 (0.00%) 
Chondrocalcinosis pyrophosphate  1  1/765 (0.13%)  0/780 (0.00%) 
Intervertebral disc disorder  1  0/765 (0.00%)  1/780 (0.13%) 
Lumbar spinal stenosis  1  1/765 (0.13%)  0/780 (0.00%) 
Muscle twitching  1  1/765 (0.13%)  0/780 (0.00%) 
Musculoskeletal chest pain  1  0/765 (0.00%)  1/780 (0.13%) 
Neck pain  1  0/765 (0.00%)  1/780 (0.13%) 
Rotator cuff syndrome  1  0/765 (0.00%)  1/780 (0.13%) 
Spinal column stenosis  1  1/765 (0.13%)  0/780 (0.00%) 
Spinal pain  1  1/765 (0.13%)  0/780 (0.00%) 
Synovial cyst  1  1/765 (0.13%)  0/780 (0.00%) 
Synovitis  1  1/765 (0.13%)  0/780 (0.00%) 
Tendonitis  1  0/765 (0.00%)  1/780 (0.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  2/765 (0.26%)  6/780 (0.77%) 
Basal cell carcinoma  1  2/765 (0.26%)  4/780 (0.51%) 
Breast cancer  1  2/765 (0.26%)  0/780 (0.00%) 
Colon cancer  1  2/765 (0.26%)  1/780 (0.13%) 
Rectal cancer  1  2/765 (0.26%)  0/780 (0.00%) 
Uterine leiomyoma  1  0/765 (0.00%)  2/780 (0.26%) 
Acute myeloid leukaemia  1  0/765 (0.00%)  1/780 (0.13%) 
Adenocarcinoma pancreas  1  1/765 (0.13%)  0/780 (0.00%) 
Endometrial adenocarcinoma  1  1/765 (0.13%)  0/780 (0.00%) 
Glioblastoma  1  0/765 (0.00%)  1/780 (0.13%) 
Hepatic cancer  1  0/765 (0.00%)  1/780 (0.13%) 
Invasive lobular breast carcinoma  1  0/765 (0.00%)  1/780 (0.13%) 
Laryngeal squamous cell carcinoma  1  1/765 (0.13%)  0/780 (0.00%) 
Lung adenocarcinoma  1  0/765 (0.00%)  1/780 (0.13%) 
Lung adenocarcinoma stage IV  1  1/765 (0.13%)  0/780 (0.00%) 
Lung neoplasm malignant  1  0/765 (0.00%)  1/780 (0.13%) 
Malignant melanoma  1  1/765 (0.13%)  0/780 (0.00%) 
Malignant melanoma in situ  1  1/765 (0.13%)  0/780 (0.00%) 
Malignant peritoneal neoplasm  1  1/765 (0.13%)  0/780 (0.00%) 
Melanoma recurrent  1  0/765 (0.00%)  1/780 (0.13%) 
Meningioma  1  1/765 (0.13%)  0/780 (0.00%) 
Metastases to bone  1  1/765 (0.13%)  0/780 (0.00%) 
Metastases to central nervous system  1  0/765 (0.00%)  1/780 (0.13%) 
Metastases to liver  1  1/765 (0.13%)  0/780 (0.00%) 
Metastatic ocular melanoma  1  0/765 (0.00%)  1/780 (0.13%) 
Nasal neoplasm benign  1  1/765 (0.13%)  0/780 (0.00%) 
Non-small cell lung cancer  1  0/765 (0.00%)  1/780 (0.13%) 
Pancreatic carcinoma  1  1/765 (0.13%)  0/780 (0.00%) 
Paranasal sinus benign neoplasm  1  1/765 (0.13%)  0/780 (0.00%) 
Renal cell carcinoma  1  1/765 (0.13%)  0/780 (0.00%) 
Renal neoplasm  1  0/765 (0.00%)  1/780 (0.13%) 
Squamous cell carcinoma  1  1/765 (0.13%)  1/780 (0.13%) 
Transitional cell carcinoma  1  0/765 (0.00%)  1/780 (0.13%) 
Uterine cancer  1  0/765 (0.00%)  1/780 (0.13%) 
Nervous system disorders     
Cerebrovascular accident  1  8/765 (1.05%)  2/780 (0.26%) 
Carpal tunnel syndrome  1  1/765 (0.13%)  2/780 (0.26%) 
Cerebral haemorrhage  1  0/765 (0.00%)  2/780 (0.26%) 
Dizziness  1  2/765 (0.26%)  0/780 (0.00%) 
Ischaemic stroke  1  2/765 (0.26%)  2/780 (0.26%) 
Transient ischaemic attack  1  2/765 (0.26%)  2/780 (0.26%) 
Brain stem infarction  1  0/765 (0.00%)  1/780 (0.13%) 
Carotid artery stenosis  1  1/765 (0.13%)  0/780 (0.00%) 
Cerebral infarction  1  0/765 (0.00%)  1/780 (0.13%) 
Cerebrovascular disorder  1  1/765 (0.13%)  0/780 (0.00%) 
Diabetic coma  1  0/765 (0.00%)  1/780 (0.13%) 
Headache  1  1/765 (0.13%)  0/780 (0.00%) 
Lacunar infarction  1  0/765 (0.00%)  1/780 (0.13%) 
Myasthenia gravis  1  1/765 (0.13%)  0/780 (0.00%) 
Myelopathy  1  1/765 (0.13%)  0/780 (0.00%) 
Optic neuritis  1  0/765 (0.00%)  1/780 (0.13%) 
Paraesthesia  1  1/765 (0.13%)  0/780 (0.00%) 
Partial seizures  1  1/765 (0.13%)  0/780 (0.00%) 
Radicular pain  1  1/765 (0.13%)  0/780 (0.00%) 
Seizure  1  0/765 (0.00%)  1/780 (0.13%) 
Subarachnoid haemorrhage  1  0/765 (0.00%)  1/780 (0.13%) 
Syncope  1  1/765 (0.13%)  1/780 (0.13%) 
Thalamic infarction  1  1/765 (0.13%)  0/780 (0.00%) 
Trigeminal neuralgia  1  1/765 (0.13%)  0/780 (0.00%) 
Psychiatric disorders     
Adjustment disorder  1  1/765 (0.13%)  0/780 (0.00%) 
Completed suicide  1  0/765 (0.00%)  1/780 (0.13%) 
Delusional disorder, unspecified type  1  1/765 (0.13%)  0/780 (0.00%) 
Depression  1  0/765 (0.00%)  1/780 (0.13%) 
Mental disorder  1  1/765 (0.13%)  0/780 (0.00%) 
Suicide attempt  1  0/765 (0.00%)  1/780 (0.13%) 
Renal and urinary disorders     
Acute kidney injury  1  0/765 (0.00%)  2/780 (0.26%) 
Nephrolithiasis  1  1/765 (0.13%)  2/780 (0.26%) 
Renal failure  1  1/765 (0.13%)  2/780 (0.26%) 
Bladder prolapse  1  1/765 (0.13%)  0/780 (0.00%) 
Calculus ureteric  1  1/765 (0.13%)  1/780 (0.13%) 
Haematuria  1  1/765 (0.13%)  0/780 (0.00%) 
Renal cyst  1  1/765 (0.13%)  0/780 (0.00%) 
Urinary tract obstruction  1  1/765 (0.13%)  0/780 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  4/765 (0.52%)  3/780 (0.38%) 
Menorrhagia  1  2/765 (0.26%)  0/780 (0.00%) 
Balanoposthitis  1  1/765 (0.13%)  0/780 (0.00%) 
Dysfunctional uterine bleeding  1  1/765 (0.13%)  0/780 (0.00%) 
Endometrial hyperplasia  1  0/765 (0.00%)  1/780 (0.13%) 
Metrorrhagia  1  0/765 (0.00%)  1/780 (0.13%) 
Prostatism  1  1/765 (0.13%)  0/780 (0.00%) 
Uterine prolapse  1  1/765 (0.13%)  1/780 (0.13%) 
Vaginal prolapse  1  1/765 (0.13%)  0/780 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  2/765 (0.26%)  1/780 (0.13%) 
Dyspnoea  1  2/765 (0.26%)  1/780 (0.13%) 
Pulmonary embolism  1  2/765 (0.26%)  0/780 (0.00%) 
Dysphonia  1  0/765 (0.00%)  1/780 (0.13%) 
Dyspnoea exertional  1  0/765 (0.00%)  1/780 (0.13%) 
Lung consolidation  1  1/765 (0.13%)  0/780 (0.00%) 
Nasal obstruction  1  1/765 (0.13%)  0/780 (0.00%) 
Paranasal cyst  1  1/765 (0.13%)  0/780 (0.00%) 
Pleural effusion  1  1/765 (0.13%)  0/780 (0.00%) 
Pneumonia aspiration  1  1/765 (0.13%)  0/780 (0.00%) 
Pneumothorax  1  1/765 (0.13%)  0/780 (0.00%) 
Respiratory failure  1  0/765 (0.00%)  1/780 (0.13%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  1/765 (0.13%)  1/780 (0.13%) 
Skin ulcer  1  0/765 (0.00%)  1/780 (0.13%) 
Surgical and medical procedures     
Arrhythmia prophylaxis  1  1/765 (0.13%)  0/780 (0.00%) 
Cholecystectomy  1  0/765 (0.00%)  1/780 (0.13%) 
Hip arthroplasty  1  1/765 (0.13%)  0/780 (0.00%) 
Hysterectomy  1  1/765 (0.13%)  1/780 (0.13%) 
Knee arthroplasty  1  0/765 (0.00%)  1/780 (0.13%) 
Omentectomy  1  1/765 (0.13%)  0/780 (0.00%) 
Oophorectomy bilateral  1  1/765 (0.13%)  0/780 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/765 (0.00%)  1/780 (0.13%) 
Hypertension  1  1/765 (0.13%)  1/780 (0.13%) 
Hypertensive emergency  1  1/765 (0.13%)  0/780 (0.00%) 
Orthostatic hypotension  1  1/765 (0.13%)  1/780 (0.13%) 
Peripheral arterial occlusive disease  1  0/765 (0.00%)  1/780 (0.13%) 
Peripheral artery stenosis  1  0/765 (0.00%)  1/780 (0.13%) 
Peripheral ischaemia  1  0/765 (0.00%)  1/780 (0.13%) 
Thrombophlebitis  1  0/765 (0.00%)  1/780 (0.13%) 
Varicose vein  1  0/765 (0.00%)  1/780 (0.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empa 25mg Glimepiride
Affected / at Risk (%) Affected / at Risk (%)
Total   580/765 (75.82%)   637/780 (81.67%) 
Gastrointestinal disorders     
Diarrhoea  1  62/765 (8.10%)  67/780 (8.59%) 
Infections and infestations     
Urinary tract infection  1  137/765 (17.91%)  121/780 (15.51%) 
Nasopharyngitis  1  90/765 (11.76%)  106/780 (13.59%) 
Upper respiratory tract infection  1  103/765 (13.46%)  97/780 (12.44%) 
Influenza  1  71/765 (9.28%)  73/780 (9.36%) 
Bronchitis  1  34/765 (4.44%)  64/780 (8.21%) 
Gastroenteritis  1  38/765 (4.97%)  47/780 (6.03%) 
Pharyngitis  1  42/765 (5.49%)  44/780 (5.64%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  41/765 (5.36%)  228/780 (29.23%) 
Hyperglycaemia  1  152/765 (19.87%)  227/780 (29.10%) 
Dyslipidaemia  1  51/765 (6.67%)  48/780 (6.15%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  93/765 (12.16%)  90/780 (11.54%) 
Arthralgia  1  70/765 (9.15%)  86/780 (11.03%) 
Pain in extremity  1  51/765 (6.67%)  50/780 (6.41%) 
Musculoskeletal pain  1  43/765 (5.62%)  43/780 (5.51%) 
Osteoarthritis  1  23/765 (3.01%)  41/780 (5.26%) 
Nervous system disorders     
Headache  1  59/765 (7.71%)  68/780 (8.72%) 
Dizziness  1  62/765 (8.10%)  67/780 (8.59%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  53/765 (6.93%)  62/780 (7.95%) 
Vascular disorders     
Hypertension  1  55/765 (7.19%)  105/780 (13.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
It should be noted that not all patients were followed up for 4 years with regard to the frequencies of adverse events presented up to 4 years.
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.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
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: NCT01167881     History of Changes
Other Study ID Numbers: 1245.28
2009-016244-39 ( EudraCT Number: EudraCT )
First Submitted: July 15, 2010
First Posted: July 22, 2010
Results First Submitted: July 17, 2014
Results First Posted: August 8, 2014
Last Update Posted: September 2, 2016