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Trial record 39 of 187 for:    BI10773

Efficacy and Safety of BI 10773 in Combination With Insulin 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: NCT01011868
Recruitment Status : Completed
First Posted : November 11, 2009
Results First Posted : September 30, 2014
Last Update Posted : September 30, 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
Condition Diabetes Mellitus, Type 2
Interventions Drug: BI 10773 placebo
Drug: BI 10773 low dose
Drug: BI 10773 high dose
Enrollment 494
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description Oral Placebo Empagliflozin 10 mg orally once daily Empagliflozin 25 mg orally once daily
Period Title: After Week 18 Follow-up
Started 170 169 155
Completed 147 153 129
Not Completed 23 16 26
Reason Not Completed
Adverse Event             8             6             13
Lack of Efficacy             1             0             0
Protocol Violation             1             1             1
Lost to Follow-up             5             3             0
Withdrawal by Subject             6             3             0
Other reason not defined above             2             3             12
Period Title: After Week 78 Follow-up
Started 170 169 155
Completed 118 131 111
Not Completed 52 38 44
Reason Not Completed
Adverse Event             14             18             21
Lack of Efficacy             4             0             0
Protocol Violation             9             1             2
Lost to Follow-up             11             6             4
Withdrawal by Subject             9             8             1
Other reason not defined above             5             5             16
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg Total
Hide Arm/Group Description Oral Placebo Empagliflozin 10 mg orally once daily Empagliflozin 25 mg orally once daily Total of all reporting groups
Overall Number of Baseline Participants 170 169 155 494
Hide Baseline Analysis Population Description
Full analysis set (FAS) – including all randomized and treated patients who had a baseline HbA1c value. Treatment assignment as randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 170 participants 169 participants 155 participants 494 participants
58.1  (9.4) 58.6  (9.8) 59.9  (10.5) 58.8  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 169 participants 155 participants 494 participants
Female
80
  47.1%
76
  45.0%
62
  40.0%
218
  44.1%
Male
90
  52.9%
93
  55.0%
93
  60.0%
276
  55.9%
1.Primary Outcome
Title Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment
Hide Description Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment
Time Frame Baseline and 18 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS18-completers-included FAS patients not prematurely discontinue prior to Week 18, completed required minimum treatment duration, and had an on treatment HbA1c value within Week 18 time window. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF-18) was used for imputation.

(LOCF-18)

Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 125 132 117
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
0.03  (0.07) -0.58  (0.07) -0.75  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

The null and alternative hypotheses to be tested:

  • H0,1: No difference in change from baseline to Week 18 in HbA1c between empagliflozin 10 mg and placebo
  • H1,1: 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 Hypotheses were tested at significance level of 0.025, which is half of overall alpha of 0.05, split equally between 2 treatment comparisons. This maintained the overall type-I (alpha) at 5%. There was no a priori assumption on testing order.
Method ANCOVA
Comments ANCOVA that included treatment group and geographic region as fixed effects along with baseline HbA1c as covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.56
Confidence Interval (2-Sided) 97.5%
-0.78 to -0.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments The primary analysis consisted of the pair-wise comparisons between each dose of empagliflozin versus placebo using the adjusted means from the model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

The null and alternative hypotheses to be tested:

  • H0,2: No difference in change from baseline to Week 18 in HbA1c between empagliflozin 25 mg and placebo
  • H1,2: 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 Hypotheses were tested at significance level of 0.025, which is half of overall alpha of 0.05, split equally between 2 treatment comparisons. This maintained the overall type-I (alpha) at 5%. There was no a priori assumption on testing order.
Method ANCOVA
Comments ANCOVA that included treatment group and geographic region as fixed effects along with baseline HbA1c as covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.70
Confidence Interval (2-Sided) 97.5%
-0.93 to -0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments The primary analysis consisted of the pair-wise comparisons between each dose of empagliflozin versus placebo using the adjusted means from the model.
2.Secondary Outcome
Title Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment
Hide Description Patients that had a reduction in HbA1c of at least 0.5% from baseline to 18, 54 and 78 weeks of treatment
Time Frame Baseline and 18, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS with non-completers considered failure (NCF)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 170 169 155
Measure Type: Number
Unit of Measure: participants
18 weeks 27 85 73
54 weeks 30 72 69
78 weeks 27 59 61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 18 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.518
Confidence Interval (2-Sided) 95%
3.262 to 9.334
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 18 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.883
Confidence Interval (2-Sided) 95%
2.859 to 8.338
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 54 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.471
Confidence Interval (2-Sided) 95%
2.077 to 5.802
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 54 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.825
Confidence Interval (2-Sided) 95%
2.268 to 6.451
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 78 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.802
Confidence Interval (2-Sided) 95%
1.639 to 4.789
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 78 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.527
Confidence Interval (2-Sided) 95%
2.051 to 6.066
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment
Hide Description Change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment
Time Frame Baseline, 18, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS observed cases (OC)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 135 138 120
Mean (Standard Error)
Unit of Measure: mg/dL
week 18 Change from BL 9.81  (5.48) -14.79  (3.93) -27.03  (3.92)
week 54 Change from BL (N=103,111,99) 0.91  (5.08) -9.59  (4.69) -23.75  (4.62)
week 78 Change from BL (N=92,104,92) -5.53  (4.95) -7.75  (4.66) -21.62  (5.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 18 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -28.40
Confidence Interval (2-Sided) 95%
-37.54 to -19.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.65
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 18 - Empagliflozin 25 mg vs Placebo at 18 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -34.21
Confidence Interval (2-Sided) 95%
-43.67 to -24.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.81
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 54 - Empagliflozin 10 mg vs Placebo at 18 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0328
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -10.75
Confidence Interval (2-Sided) 95%
-20.62 to -0.89
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.02
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 54 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -19.16
Confidence Interval (2-Sided) 95%
-29.31 to -9.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.16
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 78 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3216
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -5.03
Confidence Interval (2-Sided) 95%
-15.01 to 4.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.07
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 78 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0229
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -11.95
Confidence Interval (2-Sided) 95%
-22.24 to -1.67
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.23
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment
Hide Description Percent change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment
Time Frame Baseline, 18, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (OC)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 135 138 120
Mean (Standard Error)
Unit of Measure: percentage of Change from BL in FPG
week 18 % CHG 19.02  (6.32) -2.80  (3.17) -13.43  (2.39)
week 54 % CHG (N=103,111,99) 9.67  (5.58) 0.67  (4.05) -11.59  (3.04)
week 78 % CHG (N=92,104,92) 4.75  (5.67) 2.43  (4.18) -9.52  (3.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 18 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -25.12
Confidence Interval (2-Sided) 95%
-35.38 to -14.86
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 18 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -31.01
Confidence Interval (2-Sided) 95%
-41.62 to -20.39
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 54 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0484
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -10.20
Confidence Interval (2-Sided) 95%
-20.33 to -0.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 54 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -19.42
Confidence Interval (2-Sided) 95%
-29.84 to -8.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.30
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 78 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3517
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -4.73
Confidence Interval 95%
-14.71 to 5.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.07
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 78 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0185
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline FPG, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -12.39
Confidence Interval (2-Sided) 95%
-22.69 to -2.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.23
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment
Hide Description Change from baseline in basal insulin dose/day after 54 and 78 weeks of treatment
Time Frame Baseline, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (OC-78) for week 54 FAS78-completers (LOCF-78) for week 78 - Values after start of antidiabetic rescue therapy except changes in basal insulin dose were set to missing and last observation carried forward (LOCF) was used for imputation of missing values
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 112 127 110
Mean (Standard Error)
Unit of Measure: IU
week 54 (N=112,122,104) 5.39  (1.60) -1.20  (1.40) -1.12  (1.27)
week 78 4.79  (2.06) -0.70  (1.85) -0.39  (1.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin versus Placebo 10 mg at 54 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0213
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -5.58
Confidence Interval (2-Sided) 95%
-10.32 to -0.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.40
Estimation Comments Week 54 model includes, baseline basal insulin, baseline HbA1c as linear covariate(s), geographical region, treatment, visit and visit by treatment interaction as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin versus Placebo 25 mg at 54 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -5.69
Confidence Interval (2-Sided) 95%
-10.62 to -0.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.49
Estimation Comments Week 54 model includes, baseline basal insulin, baseline HbA1c as linear covariate(s), geographical region, treatment, visit and visit by treatment interaction as fixed effect(s).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

Empagliflozin versus Placebo 10 mg at 78 weeks

H0,1a: No difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 10 mg and placebo H1,1a: A difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 10 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments Hierarchical testing approach was applied to Empagliflozin 10 mg vs Placebo. If null hypothesis is rejected for the primary endpoint, at 0.025 (2-sided), testing of the key secondary endpoints continued in a hierarchical fashion for the same dose.
Method ANCOVA
Comments Model for Week 78 includes baseline basal insulin, baseline HbA1c as linear covariate(s) and geographical region, treatment as fixed effect(s)
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -6.66
Confidence Interval (2-Sided) 97.5%
-11.56 to -1.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

Empagliflozin versus Placebo 25 mg at 78 weeks

H0,1a: No difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 25 mg and placebo H1,1a: A difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 25 mg and placebo

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0090
Comments Hierarchical testing approach was applied to Empagliflozin 25 mg vs Placebo. If null hypothesis is rejected for the primary endpoint, at 0.025 (2-sided), testing of the key secondary endpoints continued in a hierarchical fashion for the same dose.
Method ANCOVA
Comments Model for Week 78 includes baseline basal insulin, baseline HbA1c as linear covariate(s) and geographical region, treatment as fixed effect(s)
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -5.92
Confidence Interval (2-Sided) 97.5%
-11.00 to -0.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.25
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment
Hide Description Change from baseline in body weight after 18, 54 and 78 weeks of treatment
Time Frame Baseline, 18, 54, 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (OC)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 141 148 125
Mean (Standard Error)
Unit of Measure: kg
18 weeks -0.04  (0.21) -2.06  (0.22) -0.91  (1.27)
54 weeks (N=114,120,106) -0.52  (0.32) -2.28  (0.33) -2.23  (0.35)
78 weeks (N=100,113,96) 1.12  (1.28) -2.61  (0.31) -1.99  (0.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 18 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0320
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -2.04
Confidence Interval (2-Sided) 95%
-3.90 to -0.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.95
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 18 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3818
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-2.81 to 1.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.99
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 54 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -1.97
Confidence Interval (2-Sided) 95%
-2.89 to -1.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.47
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 54 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -2.17
Confidence Interval (2-Sided) 95%
-3.13 to -1.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.49
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 78 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -3.63
Confidence Interval (2-Sided) 95%
-5.81 to -1.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.10
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 78 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes, baseline weight, baseline HbA1c as covariates, geographic region, treatment, visit and visit by treatment interaction as fixed effects
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -3.12
Confidence Interval (2-Sided) 95%
-5.39 to -0.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.15
Estimation Comments Model includes baseline weight, baseline HbA1c as linear covariates, geographical region, treatment, visit and visit by treatment interaction as fixed effects
7.Secondary Outcome
Title Change From Baseline in Body Weight at Follow-up
Hide Description Change from baseline in body weight at follow up (82 weeks)
Time Frame Baseline and 82 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-FU (OR)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 111 119 112
Mean (Standard Deviation)
Unit of Measure: kg
Follow-up 90.56  (25.87) 90.44  (19.35) 93.98  (20.87)
Follow-up change from baseline 0.92  (12.20) -2.02  (4.04) -1.05  (3.96)
Change from last value on treatment N=111,118,109 -0.23  (16.84) 0.62  (2.11) 1.34  (1.90)
8.Secondary Outcome
Title Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment
Hide Description Change from baseline in HbA1c after 54 and 78 weeks of treatment
Time Frame Baseline, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 54 - FAS (OC-78) Week 78 - FAS78-completers (LOCF-78)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 113 127 110
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
Week 54 (N=113,121,107) -0.06  (0.08) -0.59  (0.08) -0.84  (0.09)
Week 78 (N=112,127,110) -0.05  (0.10) -0.51  (0.09) -0.68  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Change from BL at week 54 - Empagliflozin 10 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.68 to -0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Model includes baseline HbA1c as linear covariate(s), geographical region, treatment, visit and visit by treatment interaction as fixed effect(s).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Change from BL at week 54 - Empagliflozin 25 mg vs Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-0.95 to -0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments Model includes baseline HbA1c as linear covariate(s), geographical region, treatment, visit and visit by treatment interaction as fixed effect(s).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments

Change from BL at week 78 - Empagliflozin 10 mg vs Placebo

H0,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 10 mg and placebo ≥0.3% H1,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 10 mg and placebo <0.3%

Type of Statistical Test Non-Inferiority or Equivalence
Comments

For non-inferiority, a one-sided test at the significance level of 0.0125 was performed using a chosen margin of 0.3% difference between each dose of empagliflozin and placebo.

If the non-inferiority of empagliflozin to placebo with respect to change from baseline in HbA1c after 78 weeks of treatment could be concluded for a specific dose, subsequent testing of superiority was performed at the significance level of 0.025 for the relevant empagliflozin dose versus placebo comparison.

Statistical Test of Hypothesis P-Value 0.0001
Comments Hierarchical testing approach was applied to Empagliflozin 10 mg vs Placebo. If null hypothesis is rejected for the primary endpoint, at 0.025 (2-sided), testing of the key secondary endpoints continued in a hierarchical fashion for the same dose.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.46
Confidence Interval (2-Sided) 97.5%
-0.73 to -0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Model includes baseline HbA1c as linear covariate(s), geographical region, treatment as fixed effect(s).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments

Change from BL at week 78 - Empagliflozin 25 mg vs Placebo

H0,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 25 mg and placebo ≥0.3% H1,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 25 mg and placebo <0.3%

Type of Statistical Test Non-Inferiority or Equivalence
Comments

For non-inferiority, a one-sided test at the significance level of 0.0125 was performed using a chosen margin of 0.3% difference between each dose of empagliflozin and placebo.

If the non-inferiority of empagliflozin to placebo with respect to change from baseline in HbA1c after 78 weeks of treatment could be concluded for a specific dose, subsequent testing of superiority was performed at the significance level of 0.025 for the relevant empagliflozin dose versus placebo comparison.

Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing approach was applied to Empagliflozin 25 mg vs Placebo. If null hypothesis is rejected for the primary endpoint, at 0.025 (2-sided), testing of the key secondary endpoints continued in a hierarchical fashion for the same dose.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.62
Confidence Interval (2-Sided) 97.5%
-0.90 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Model includes baseline HbA1c as linear covariate(s), geographical region, treatment as fixed effect(s).
9.Secondary Outcome
Title The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment
Hide Description The occurrence of treat to target efficacy response, that is an HbA1c under treatment of <7.0% After 18, 54, and 78 weeks of treatment
Time Frame Baseline, 18, 54 and 78 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (NCF)
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 165 167 154
Measure Type: Number
Unit of Measure: participants
18 weeks 9 30 30
54 weeks 14 23 27
78 weeks 11 20 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 18 weeks
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 Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.096
Confidence Interval (2-Sided) 95%
1.846 to 9.088
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 18 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.636
Confidence Interval (2-Sided) 95%
2.083 to 10.321
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 54 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1248
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.750
Confidence Interval (2-Sided) 95%
0.856 to 3.575
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 54 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0132
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.423
Confidence Interval (2-Sided) 95%
1.203 to 4.879
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 10 mg
Comments Empagliflozin 10 mg vs Placebo at 78 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0986
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.939
Confidence Interval (2-Sided) 95%
0.884 to 4.256
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Empagliflozin 25 mg
Comments Empagliflozin 25 mg vs Placebo at 78 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression includes treatment, geographical region and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.239
Confidence Interval (2-Sided) 95%
1.518 to 6.911
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Confirmed Hypoglycemic Events
Hide Description Confirmed hypoglycemic events refer to all hypoglycemic events that had a glucose value ≤70 ml/dL or where assistance was required. Symptomatic hypoglycemic events were to be reported as adverse events. Investigator-defined hypoglycaemia adverse events include all events that investigator marked as ‘Hypoglycaemic event’ in CRFs, regardless of the reported term or blood glucose value. It may include hypoglycemia itself as reported term or any other symptoms that that investigator may have attributed to hypoglycemia (e.g. dizziness, hyperhidrosis, and asthenia).
Time Frame During the course of the study (82 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set (TS). Treatment assignment as first medication taken.
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description:
Oral Placebo
Empagliflozin 10 mg orally once daily
Empagliflozin 25 mg orally once daily
Overall Number of Participants Analyzed 170 169 155
Measure Type: Number
Unit of Measure: participants
60 61 56
Time Frame During the course of the study (82 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Empagliflozin 10 mg Empagliflozin 25 mg
Hide Arm/Group Description Oral Placebo Empagliflozin 10 mg orally once daily Empagliflozin 25 mg orally 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   28/170 (16.47%)   28/169 (16.57%)   28/155 (18.06%) 
Cardiac disorders       
Bradycardia  1  0/170 (0.00%)  2/169 (1.18%)  0/155 (0.00%) 
Coronary artery disease  1  2/170 (1.18%)  2/169 (1.18%)  0/155 (0.00%) 
Acute myocardial infarction  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Angina pectoris  1  1/170 (0.59%)  1/169 (0.59%)  0/155 (0.00%) 
Angina unstable  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Atrial fibrillation  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Atrial flutter  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Cardiac arrest  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Coronary artery occlusion  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Myocardial infarction  1  0/170 (0.00%)  1/169 (0.59%)  1/155 (0.65%) 
Myocardial ischaemia  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Right ventricular failure  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Congenital, familial and genetic disorders       
Arnold-Chiari malformation  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Eye disorders       
Macular fibrosis  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Retinal detachment  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Vitreous haemorrhage  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Constipation  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Enterocutaneous fistula  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Gastric ulcer haemorrhage  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Haematochezia  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Oesophageal ulcer  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Oesophagitis  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Pancreatitis acute  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Rectal haemorrhage  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
General disorders       
Chest discomfort  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Chest pain  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Device failure  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Non-cardiac chest pain  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Infections and infestations       
Cystitis  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Diverticulitis  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Enterocolitis infectious  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Osteomyelitis  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Pneumonia  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Pyelonephritis  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Scrotal abscess  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Sepsis  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Sinusitis  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Urinary tract infection  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Injury, poisoning and procedural complications       
Road traffic accident  1  0/170 (0.00%)  2/169 (1.18%)  0/155 (0.00%) 
Accident at home  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Accident at work  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Concussion  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Contusion  1  0/170 (0.00%)  1/169 (0.59%)  1/155 (0.65%) 
Fall  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Ligament sprain  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Limb crushing injury  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Overdose  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Radius fracture  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Skeletal injury  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Wrist fracture  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Investigations       
Hepatic enzyme increased  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Metabolism and nutrition disorders       
Dehydration  1  1/170 (0.59%)  1/169 (0.59%)  0/155 (0.00%) 
Hypoglycaemia  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Hypovolaemia  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  0/170 (0.00%)  2/169 (1.18%)  1/155 (0.65%) 
Arthralgia  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Costochondritis  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Joint contracture  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Joint instability  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Musculoskeletal stiffness  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Rotator cuff syndrome  1  1/170 (0.59%)  1/169 (0.59%)  0/155 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Thyroid cancer  1  0/170 (0.00%)  0/169 (0.00%)  2/155 (1.29%) 
Prostate cancer  1  2/170 (1.18%)  0/169 (0.00%)  0/155 (0.00%) 
Bladder cancer  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Breast cancer  1  1/170 (0.59%)  1/169 (0.59%)  0/155 (0.00%) 
Colon cancer  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Gastric cancer  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Lung neoplasm malignant  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Malignant fibrous histiocytoma  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Mycosis fungoides  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Pancreatic carcinoma  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Prostatic adenoma  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Squamous cell carcinoma of the cervix  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Nervous system disorders       
Syncope  1  0/170 (0.00%)  2/169 (1.18%)  0/155 (0.00%) 
Carotid artery occlusion  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Carotid artery stenosis  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Cerebral haemorrhage  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Cerebral infarction  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Cerebrovascular accident  1  0/170 (0.00%)  1/169 (0.59%)  1/155 (0.65%) 
Convulsion  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Haemorrhagic stroke  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Sciatica  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Transient ischaemic attack  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Psychiatric disorders       
Depression  1  1/170 (0.59%)  1/169 (0.59%)  0/155 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  2/170 (1.18%)  0/169 (0.00%)  0/155 (0.00%) 
Nephrotic syndrome  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Neurogenic bladder  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Renal failure  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Renal failure acute  1  0/170 (0.00%)  1/169 (0.59%)  1/155 (0.65%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Dyspnoea  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Vocal cord polyp  1  0/170 (0.00%)  1/169 (0.59%)  0/155 (0.00%) 
Skin and subcutaneous tissue disorders       
Skin ulcer  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Surgical and medical procedures       
Carotid endarterectomy  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Vascular disorders       
Femoral arterial stenosis  1  0/170 (0.00%)  0/169 (0.00%)  1/155 (0.65%) 
Orthostatic hypotension  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Peripheral vascular disorder  1  1/170 (0.59%)  0/169 (0.00%)  0/155 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
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   115/170 (67.65%)   110/169 (65.09%)   95/155 (61.29%) 
Gastrointestinal disorders       
Diarrhoea  1  13/170 (7.65%)  10/169 (5.92%)  11/155 (7.10%) 
Nausea  1  12/170 (7.06%)  9/169 (5.33%)  8/155 (5.16%) 
Vomiting  1  5/170 (2.94%)  4/169 (2.37%)  8/155 (5.16%) 
General disorders       
Fatigue  1  2/170 (1.18%)  10/169 (5.92%)  4/155 (2.58%) 
Infections and infestations       
Nasopharyngitis  1  22/170 (12.94%)  20/169 (11.83%)  17/155 (10.97%) 
Urinary tract infection  1  13/170 (7.65%)  21/169 (12.43%)  16/155 (10.32%) 
Upper respiratory tract infection  1  10/170 (5.88%)  18/169 (10.65%)  13/155 (8.39%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  56/170 (32.94%)  56/169 (33.14%)  55/155 (35.48%) 
Hyperglycaemia  1  17/170 (10.00%)  16/169 (9.47%)  15/155 (9.68%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  13/170 (7.65%)  11/169 (6.51%)  13/155 (8.39%) 
Arthralgia  1  9/170 (5.29%)  6/169 (3.55%)  8/155 (5.16%) 
Nervous system disorders       
Dizziness  1  12/170 (7.06%)  18/169 (10.65%)  7/155 (4.52%) 
Headache  1  5/170 (2.94%)  5/169 (2.96%)  8/155 (5.16%) 
Psychiatric disorders       
Depression  1  3/170 (1.76%)  10/169 (5.92%)  2/155 (1.29%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  9/170 (5.29%)  6/169 (3.55%)  4/155 (2.58%) 
Vascular disorders       
Hypertension  1  12/170 (7.06%)  1/169 (0.59%)  3/155 (1.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
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: NCT01011868     History of Changes
Other Study ID Numbers: 1245.33
2009-013668-38 ( EudraCT Number: EudraCT )
First Submitted: November 10, 2009
First Posted: November 11, 2009
Results First Submitted: May 16, 2014
Results First Posted: September 30, 2014
Last Update Posted: September 30, 2014