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Safety and Efficacy of BI 10773 as add-on to Insulin Regimen in Patients With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT01306214
Recruitment Status : Completed
First Posted : March 1, 2011
Results First Posted : June 17, 2014
Last Update Posted : June 17, 2014
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
Conditions Diabetes Mellitus, Type 2
Obesity
Interventions Drug: Placebo
Drug: BI 10773
Enrollment 566
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Period Title: Overall Study
Started 189 187 190
Completed 161 159 168
Not Completed 28 28 22
Reason Not Completed
Death             0             0             1
Lost to Follow-up             3             5             4
Withdrawal by Subject             24             22             16
Not treated             1             1             1
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg Total
Hide Arm/Group Description Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily Total of all reporting groups
Overall Number of Baseline Participants 188 186 189 563
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): FAS included all randomised and treated patients who had a baseline HbA1c value.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 188 participants 186 participants 189 participants 563 participants
55.3  (10.1) 56.7  (8.7) 58.0  (9.4) 56.7  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 188 participants 186 participants 189 participants 563 participants
Female
113
  60.1%
89
  47.8%
105
  55.6%
307
  54.5%
Male
75
  39.9%
97
  52.2%
84
  44.4%
256
  45.5%
1.Primary Outcome
Title Change From Baseline in HbA1c After 18 Weeks of Treatment
Hide Description The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment.
Time Frame Baseline and 18 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted on the full analysis set (FAS) of patients. Values after start of antidiabetic rescue therapy (week 18 definition) were set to missing and last observation carried forward (LOCF-18) was used for imputation of missing values.
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Number of Participants Analyzed 188 186 189
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.50  (0.05) -0.94  (0.05) -1.02  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

For the primary endpoint, the testing of the superiority hypothesis versus placebo was:

Hypothesis test:

H0: No difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing to adjust for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 18 was the first step in each hierarchical sequence.
Method ANCOVA
Comments ANCOVA Model includes baseline HbA1c as a covariate and baseline eGFR, geographic region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.44
Confidence Interval (2-Sided) 97.5%
-0.61 to -0.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.08
Estimation Comments Estimated value = Adjusted mean of Empagliflozin 10 mg - Adjusted mean of placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

For the primary endpoint, the testing of the superiority hypothesis versus placebo was:

H0: No difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 25 mg and placebo Ha: A difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 25 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing to adjust for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 18 was the first step in each hierarchical sequence.
Method ANCOVA
Comments ANCOVA Model includes baseline HbA1c as a covariate and baseline eGFR, geographic region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.52
Confidence Interval (2-Sided) 97.5%
-0.69 to -0.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.07
Estimation Comments Estimated value = Adjusted mean of Empagliflozin 25 mg - Adjusted mean of placebo
2.Secondary Outcome
Title Change From Baseline in Insulin Dose After 52 Weeks of Treatment
Hide Description The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment
Time Frame Baseline and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set-patients in FAS without important protocol violations leading to exclusion, completed minimum treatment of 357 days and did not prematurely discontinue. Values after start of antidiabetic rescue therapy (week 52 definition) were set to missing and last observation carried forward (LOCF-52) was used for imputation of missing values.
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Number of Participants Analyzed 115 118 117
Least Squares Mean (Standard Error)
Unit of Measure: IU/day
10.16  (2.16) 1.33  (2.13) -1.06  (2.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

Hypothesis test:

H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in insulin dose at week 52 was the second step in hierarchical sequence.
Method ANCOVA
Comments Model - Covariates: baseline insulin daily dose,baseline HbA1c Fixed effects: baseline eGFR, region, baseline background medication, treatment
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -8.83
Confidence Interval (2-Sided) 97.5%
-15.69 to -1.97
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.05
Estimation Comments Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

Hypothesis test:

H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in insulin dose at week 52 was the second step in hierarchical sequence.
Method ANCOVA
Comments Model - Covariates: baseline insulin daily dose,baseline HbA1c Fixed effects: baseline eGFR, region, baseline background medication, treatment
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -11.22
Confidence Interval (2-Sided) 97.5%
-18.09 to -4.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.05
Estimation Comments Estimated value = Adjusted mean of Empagliflozin 25 mg - Adjusted mean of placebo.
3.Secondary Outcome
Title Change From Baseline in Body Weight After 52 Weeks of Treatment
Hide Description The secondary endpoint was the change from baseline in body weight after 52 weeks of treatment
Time Frame Baseline and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Number of Participants Analyzed 115 119 118
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.44  (0.36) -1.95  (0.36) -2.04  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

Hypothesis test:

H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in body weight at week 52 was the third step in hierarchical sequence.
Method ANCOVA
Comments Model includes baseline weight, baseline HbA1c as covariates and baseline eGFR, region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -2.39
Confidence Interval (2-Sided) 97.5%
-3.54 to -1.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments hypothesis test: H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebo Ha: A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in body weight at week 52 was the third step in hierarchical sequence.
Method ANCOVA
Comments Model includes baseline weight, baseline HbA1c as covariates and baseline eGFR, region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -2.48
Confidence Interval (2-Sided) 97.5%
-3.63 to -1.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.51
Estimation Comments Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo
4.Secondary Outcome
Title Change From Baseline in HbA1c After 52 Weeks of Treatment
Hide Description The secondary endpoint was the change from baseline in HbA1c after 52 weeks of treatment
Time Frame Baseline and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Number of Participants Analyzed 115 119 118
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.81  (0.08) -1.18  (0.08) -1.27  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments H0: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo >0.3 Ha: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo ≤0.3
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non- inferiority margin was 0.3%, one-sided.
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).
Method ANCOVA
Comments Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.38
Confidence Interval (2-Sided) 97.5%
-0.62 to -0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

Hypothesis test:

H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).
Method ANCOVA
Comments Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.38
Confidence Interval (2-Sided) 97.5%
-0.62 to -0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments H013: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo >0.3 Ha13: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo ≤0.3
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non- inferiority margin was 0.3%, one-sided.
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).
Method ANCOVA
Comments Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.46
Confidence Interval (2-Sided) 97.5%
-0.70 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

Hypothesis test:

H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).
Method ANCOVA
Comments Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.46
Confidence Interval (2-Sided) 97.5%
-0.70 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo
Time Frame Up to 52 weeks
Adverse Event Reporting Description An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
 
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
All-Cause Mortality
Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/188 (11.70%)   20/186 (10.75%)   22/189 (11.64%) 
Blood and lymphatic system disorders       
Anaemia  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Cardiac disorders       
Coronary artery disease  1  2/188 (1.06%)  0/186 (0.00%)  1/189 (0.53%) 
Acute myocardial infarction  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Angina pectoris  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Bundle branch block right  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Cardiac failure  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Cardiac failure congestive  1  1/188 (0.53%)  0/186 (0.00%)  1/189 (0.53%) 
Cor pulmonale  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Supraventricular tachycardia  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Tachycardia  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/188 (0.00%)  2/186 (1.08%)  1/189 (0.53%) 
Vertigo positional  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Eye disorders       
Amaurosis  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Angle closure glaucoma  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Pterygium  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/188 (0.00%)  2/186 (1.08%)  0/189 (0.00%) 
Diarrhoea  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Gastric ulcer  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Gastrointestinal haemorrhage  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Pancreatitis acute  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Small intestinal obstruction  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Umbilical hernia  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Immune system disorders       
Sarcoidosis  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Infections and infestations       
Pneumonia  1  1/188 (0.53%)  3/186 (1.61%)  1/189 (0.53%) 
Anal abscess  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Appendicitis  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Diabetic gangrene  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Gastrointestinal infection  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Lobar pneumonia  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Sepsis  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Subcutaneous abscess  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Urinary tract infection  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Injury, poisoning and procedural complications       
Concussion  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Humerus fracture  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Wound  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Diabetic ketoacidosis  1  1/188 (0.53%)  1/186 (0.54%)  0/189 (0.00%) 
Hyperglycaemia  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Hypoglycaemia  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc disorder  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Intervertebral disc protrusion  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Neuropathic arthropathy  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Osteoarthritis  1  0/188 (0.00%)  1/186 (0.54%)  1/189 (0.53%) 
Rhabdomyolysis  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Ependymoma  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Gastric cancer  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Glioblastoma  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Lung cancer metastatic  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Pancreatic carcinoma metastatic  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Prostate cancer  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Uterine leiomyoma  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Nervous system disorders       
Carpal tunnel syndrome  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Cerebrovascular accident  1  1/188 (0.53%)  1/186 (0.54%)  0/189 (0.00%) 
Cervicobrachial syndrome  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Convulsion  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Grand mal convulsion  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Migraine  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Radiculitis  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Syncope  1  0/188 (0.00%)  1/186 (0.54%)  1/189 (0.53%) 
Pregnancy, puerperium and perinatal conditions       
Ectopic pregnancy  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Psychiatric disorders       
Depression  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Renal and urinary disorders       
Acute prerenal failure  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Renal colic  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Renal failure acute  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Renal impairment  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute pulmonary oedema  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Asthma  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Chronic obstructive pulmonary disease  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Respiratory failure  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Sleep apnoea syndrome  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Skin and subcutaneous tissue disorders       
Diabetic foot  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Skin ulcer  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Surgical and medical procedures       
Vitrectomy  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Vascular disorders       
Hypertensive emergency  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (0.00%) 
Orthostatic hypotension  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Peripheral arterial occlusive disease  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Peripheral artery stenosis  1  0/188 (0.00%)  0/186 (0.00%)  1/189 (0.53%) 
Thrombophlebitis migrans  1  0/188 (0.00%)  1/186 (0.54%)  0/189 (0.00%) 
Venous thrombosis  1  1/188 (0.53%)  0/186 (0.00%)  0/189 (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%
Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   146/188 (77.66%)   135/186 (72.58%)   140/189 (74.07%) 
Gastrointestinal disorders       
Diarrhoea  1  17/188 (9.04%)  12/186 (6.45%)  17/189 (8.99%) 
Infections and infestations       
Nasopharyngitis  1  40/188 (21.28%)  34/186 (18.28%)  27/189 (14.29%) 
Urinary tract infection  1  23/188 (12.23%)  24/186 (12.90%)  24/189 (12.70%) 
Influenza  1  12/188 (6.38%)  7/186 (3.76%)  14/189 (7.41%) 
Bronchitis  1  12/188 (6.38%)  10/186 (5.38%)  8/189 (4.23%) 
Gastroenteritis  1  10/188 (5.32%)  8/186 (4.30%)  1/189 (0.53%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  111/188 (59.04%)  97/186 (52.15%)  110/189 (58.20%) 
Hyperglycaemia  1  14/188 (7.45%)  6/186 (3.23%)  7/189 (3.70%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  10/188 (5.32%)  18/186 (9.68%)  11/189 (5.82%) 
Back pain  1  14/188 (7.45%)  12/186 (6.45%)  15/189 (7.94%) 
Nervous system disorders       
Dizziness  1  2/188 (1.06%)  5/186 (2.69%)  13/189 (6.88%) 
Headache  1  9/188 (4.79%)  8/186 (4.30%)  11/189 (5.82%) 
Vascular disorders       
Hypertension  1  10/188 (5.32%)  9/186 (4.84%)  7/189 (3.70%) 
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.
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 Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01306214     History of Changes
Other Study ID Numbers: 1245.49
2010-019968-37 ( EudraCT Number: EudraCT )
First Submitted: February 28, 2011
First Posted: March 1, 2011
Results First Submitted: May 16, 2014
Results First Posted: June 17, 2014
Last Update Posted: June 17, 2014