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Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive 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: NCT01719003
Recruitment Status : Completed
First Posted : November 1, 2012
Results First Posted : February 19, 2016
Last Update Posted : February 19, 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
Conditions Diabetes Mellitus, Type 2
Hyperglycemia
Interventions Drug: Metformin 500 mg bid
Drug: Metformin 1000 mg bid
Drug: Empagliflozin low dose qd
Drug: Empagliflozin high dose qd
Drug: Empagliflozin low dose bid
Drug: Empagliflozin high dose bid
Enrollment 1413
Recruitment Details With the first global protocol amendment (13-Dec-2012), the HbA1c inclusion criterion changed and further enrolment in the open label (OL) group was stopped, but the patients already entered in the OL group could continue until the scheduled end of the study.
Pre-assignment Details Patients with an (Glycosylated Haemoglobin) HbA1c >10.0% at screening and meeting all other inclusion criteria were initially directly included in an OL treatment group
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL
Hide Arm/Group Description Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid) Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 25 mg once daily (qd) Oral administration of Empagliflozin 10 mg qd Oral administration of Metformin 1000 mg bid Oral administration of Metformin 500 mg bid Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg bid in an open label (OL)
Period Title: Overall Study
Started 170 170 171 169 167 172 170 171 53
Completed 161 153 154 156 150 160 150 151 49
Not Completed 9 17 17 13 17 12 20 20 4
Reason Not Completed
Non compliant with protocol             1             1             0             1             2             1             2             3             0
Adverse Event             6             5             4             3             4             3             6             5             0
Lost to Follow-up             0             6             7             2             3             4             3             2             2
Refusal to continue, not due to AE             2             5             4             4             4             3             8             7             1
Reason other than those specified             0             0             2             3             4             1             0             3             1
Lack of Efficacy             0             0             0             0             0             0             1             0             0
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Total
Hide Arm/Group Description Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid) Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 25 mg once daily (qd) Oral administration of Empagliflozin 10 mg qd Oral administration of Metformin 1000 mg bid Oral administration of Metformin 500 mg bid Total of all reporting groups
Overall Number of Baseline Participants 169 165 167 161 164 169 164 168 1327
Hide Baseline Analysis Population Description
Full analysis set (FAS): FAS comprised all randomised patients treated with at least 1 dose of trial medication, with a baseline and at least 1 on-treatment HbA1c assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 169 participants 165 participants 167 participants 161 participants 164 participants 169 participants 164 participants 168 participants 1327 participants
53.6  (10.7) 51.0  (10.7) 52.3  (11.3) 52.2  (11.7) 53.3  (10.7) 53.1  (10.7) 51.6  (10.8) 53.4  (10.9) 52.6  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 169 participants 165 participants 167 participants 161 participants 164 participants 169 participants 164 participants 168 participants 1327 participants
Female
81
  47.9%
60
  36.4%
68
  40.7%
64
  39.8%
81
  49.4%
72
  42.6%
72
  43.9%
82
  48.8%
580
  43.7%
Male
88
  52.1%
105
  63.6%
99
  59.3%
97
  60.2%
83
  50.6%
97
  57.4%
92
  56.1%
86
  51.2%
747
  56.3%
1.Primary Outcome
Title HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 24
Hide Description

Change from baseline in HbA1c (%) after 24 weeks of treatment.

“Baseline” refers to the last observation before the start of any randomised trial treatment medication. Means presented are the adjusted means

Time Frame baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS observed cases (OC) (Only patients with available data are analysed)
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid
Hide Arm/Group Description:
Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 25 mg once daily (qd)
Oral administration of Empagliflozin 10 mg qd
Oral administration of Metformin 1000 mg bid
Oral administration of Metformin 500 mg bid
Overall Number of Participants Analyzed 159 149 151 153 143 156 146 142
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-2.08  (0.08) -1.93  (0.08) -2.07  (0.08) -1.98  (0.08) -1.36  (0.08) -1.35  (0.08) -1.75  (0.09) -1.18  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.56 to -0.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid, Empagliflozin 25 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-0.95 to -0.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Empagliflozin 25 mg qd
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -0.75
Confidence Interval (2-Sided) 95%
-0.98 to -0.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 500 mg bid minus Metformin 500 mg bid
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid, Empagliflozin 25 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.81 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 500 mg bid minus Empagliflozin 25 mg qd
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments [Not Specified]
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.56 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 5 mg bid + Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 1000 mg Bid, Empagliflozin 10 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-0.95 to -0.49
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 5 mg bid + Metformin 1000 mg bid minus Empagliflozin 10 mg qd
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-1.03 to -0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 5 mg bid + Metformin 500 mg bid minus Metformin 500 mg bid
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 500 mg Bid, Empagliflozin 10 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
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 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.86 to -0.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 5 mg bid + Metformin 500 mg bid minus Empagliflozin 10 mg qd
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg qd, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The noninferiority of empagliflozin 10 mg qd against metformin 1000 mg bid were to be tested for HbA1c change from baseline to Week 24 at the level of α=0.025 (one-sided), through application of a non-inferiority margin of 0.35%.
Statistical Test of Hypothesis P-Value 0.6246
Comments [Not Specified]
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.15 to 0.62
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 25 mg qd minus Metformin 1000 mg bid
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Empagliflozin 10 mg qd, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The noninferiority of empagliflozin 10 mg qd against metformin 1000 mg bid were to be tested for HbA1c change from baseline to Week 24 at the level of α=0.025 (one-sided), through application of a non-inferiority margin of 0.35%.
Statistical Test of Hypothesis P-Value 0.6558
Comments [Not Specified]
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.16 to 0.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments Empagliflozin 10 mg qd minus Metformin 1000 mg bid
2.Secondary Outcome
Title FPG (Fasting Plasma Glucose) Change From Baseline at Week 24
Hide Description

Change from baseline in FPG (mg/dL) after 24 weeks of treatment.

“Baseline” refers to the last observation before the start of any randomised trial treatment medication. Means presented are the adjusted means.

Time Frame baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS observed cases (OC) (Only patients with available data are analysed)
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid
Hide Arm/Group Description:
Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 25 mg once daily (qd)
Oral administration of Empagliflozin 10 mg qd
Oral administration of Metformin 1000 mg bid
Oral administration of Metformin 500 mg bid
Overall Number of Participants Analyzed 158 146 146 153 139 154 145 139
Mean (Standard Error)
Unit of Measure: mg/dL
-51.0  (2.4) -44.0  (2.4) -47.8  (2.4) -45.5  (2.4) -28.0  (2.5) -32.9  (2.4) -32.1  (2.4) -17.2  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -18.8
Confidence Interval (2-Sided) 95%
-25.5 to -12.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid, Empagliflozin 25 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -23.0
Confidence Interval (2-Sided) 95%
-29.7 to -16.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Empagliflozin 25 mg qd
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -26.7
Confidence Interval (2-Sided) 95%
-33.5 to -20.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 500 mg bid minus Metformin 500 mg bid
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid, Empagliflozin 25 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -16.0
Confidence Interval (2-Sided) 95%
-22.8 to -9.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 500 mg bid minus Empagliflozin 25 mg qd
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG of double-blind treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -15.6
Confidence Interval (2-Sided) 95%
-22.3 to -8.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 5 mg bid + Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 1000 mg Bid, Empagliflozin 10 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -14.8
Confidence Interval (2-Sided) 95%
-21.4 to -8.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 5 mg bid + Metformin 1000 mg bid minus Empagliflozin 10 mg qd
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -28.2
Confidence Interval (2-Sided) 95%
-35.0 to -21.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 5 mg bid + Metformin 500 mg bid minus Metformin 500 mg bid
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 500 mg Bid, Empagliflozin 10 mg qd
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of FPG after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -12.6
Confidence Interval (2-Sided) 95%
-19.1 to -6.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments Empagliflozin 5 mg bid + Metformin 500 mg bid minus Empagliflozin 10 mg qd
3.Secondary Outcome
Title Body Weight Change From Baseline at Week 24
Hide Description

Change from baseline in body weight (kg) after 24 weeks of treatment.

“Baseline” refers to the last observation before the start of any randomised trial treatment. medication. Means presented are the adjusted means.

Time Frame baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS observed cases (OC) (Only patients with available data are analysed)
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid
Hide Arm/Group Description:
Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
Oral administration of Empagliflozin 25 mg once daily (qd)
Oral administration of Empagliflozin 10 mg qd
Oral administration of Metformin 1000 mg bid
Oral administration of Metformin 500 mg bid
Overall Number of Participants Analyzed 160 149 150 155 143 155 148 140
Mean (Standard Error)
Unit of Measure: kg
-3.78  (0.29) -3.04  (0.30) -3.48  (0.30) -2.77  (0.30) -2.38  (0.30) -2.39  (0.29) -1.27  (0.30) -0.52  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of body weight after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-3.33 to -1.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of body weight after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -2.52
Confidence Interval (2-Sided) 95%
-3.35 to -1.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments Empagliflozin 12.5 mg bid+ Metformin 500 mg bid minus Metformin 500 mg bid
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 1000 mg Bid, Metformin 1000 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of body weight after 24 weeks of double-blind treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted mean
Estimated Value -2.20
Confidence Interval (2-Sided) 95%
-3.03 to -1.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments Empagliflozin 5 mg bid + Metformin 1000 mg bid minus Metformin 1000 mg bid
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Empagliflozin 5 mg Bid + Metformin 500 mg Bid, Metformin 500 mg Bid
Comments Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of body weight after 24 weeks of double-blind treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Since previous step in the hierarchical testing failed (primary measure analyses 9 and 10), the analyses for secondary measures of FPG and body weight are considered exploratory and not confirmatory
Method Mixed Models Analysis
Comments 'Baseline HbA1c’:linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value -2.26
Confidence Interval (2-Sided) 95%
-3.09 to -1.43
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments Empagliflozin 5 mg bid + Metformin 500 mg bid minus Metformin 500 mg bid
Time Frame Adverse events with an onset after the first dose of randomised trial medication up to a period of 7 days after the last dose (Up to 237 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL
Hide Arm/Group Description Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid) Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid Oral administration of Empagliflozin 25 mg once daily (qd) Oral administration of Empagliflozin 10 mg qd Oral administration of Metformin 1000 mg bid Oral administration of Metformin 500 mg bid Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg bid in an open label (OL)
All-Cause Mortality
Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/170 (1.18%)   6/170 (3.53%)   3/171 (1.75%)   2/169 (1.18%)   3/167 (1.80%)   1/172 (0.58%)   3/170 (1.76%)   3/171 (1.75%)   2/53 (3.77%) 
Blood and lymphatic system disorders                   
Anaemia  1  0/170 (0.00%)  0/170 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Cardiac disorders                   
Acute myocardial infarction  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  1/172 (0.58%)  0/170 (0.00%)  1/171 (0.58%)  1/53 (1.89%) 
Tachycardia paroxysmal  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Angina unstable  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  1/53 (1.89%) 
Gastrointestinal disorders                   
Pancreatitis acute  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
General disorders                   
Chest pain  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  1/53 (1.89%) 
Hepatobiliary disorders                   
Bile duct stone  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Cholangitis acute  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Cholelithiasis  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Hepatic cirrhosis  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Infections and infestations                   
Appendicitis  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Dengue fever  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  1/171 (0.58%)  0/53 (0.00%) 
Herpes simplex encephalitis  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  1/171 (0.58%)  0/53 (0.00%) 
Nasal abscess  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Injury, poisoning and procedural complications                   
Accidental overdose  1  0/170 (0.00%)  0/170 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Rib fracture  1  0/170 (0.00%)  0/170 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Metabolism and nutrition disorders                   
Diabetes mellitus inadequate control  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/53 (0.00%) 
Hypomagnesaemia  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  1/53 (1.89%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Chronic lymphocytic leukaemia  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Uterine leiomyoma  1  1/170 (0.59%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Nervous system disorders                   
Cerebral infarction  1  1/170 (0.59%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Cerebrovascular accident  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/53 (0.00%) 
Renal and urinary disorders                   
Haematuria  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Chronic obstructive pulmonary disease  1  0/170 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Vascular disorders                   
Hypertensive crisis  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%)  0/172 (0.00%)  1/170 (0.59%)  0/171 (0.00%)  0/53 (0.00%) 
Peripheral arterial occlusive disease  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Peripheral ischaemia  1  0/170 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%)  0/172 (0.00%)  0/170 (0.00%)  0/171 (0.00%)  0/53 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Empagliflozin 5 mg Bid + Metformin 500 mg Bid Empagliflozin 25 mg qd Empagliflozin 10 mg qd Metformin 1000 mg Bid Metformin 500 mg Bid Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   48/170 (28.24%)   40/170 (23.53%)   35/171 (20.47%)   42/169 (24.85%)   41/167 (24.55%)   36/172 (20.93%)   53/170 (31.18%)   38/171 (22.22%)   16/53 (30.19%) 
Gastrointestinal disorders                   
Diarrhoea  1  12/170 (7.06%)  6/170 (3.53%)  5/171 (2.92%)  9/169 (5.33%)  6/167 (3.59%)  2/172 (1.16%)  24/170 (14.12%)  6/171 (3.51%)  4/53 (7.55%) 
Gastritis  1  0/170 (0.00%)  1/170 (0.59%)  2/171 (1.17%)  1/169 (0.59%)  2/167 (1.20%)  0/172 (0.00%)  4/170 (2.35%)  2/171 (1.17%)  3/53 (5.66%) 
Nausea  1  6/170 (3.53%)  4/170 (2.35%)  5/171 (2.92%)  5/169 (2.96%)  1/167 (0.60%)  1/172 (0.58%)  3/170 (1.76%)  1/171 (0.58%)  3/53 (5.66%) 
Infections and infestations                   
Upper respiratory tract infection  1  4/170 (2.35%)  5/170 (2.94%)  8/171 (4.68%)  4/169 (2.37%)  7/167 (4.19%)  5/172 (2.91%)  5/170 (2.94%)  10/171 (5.85%)  3/53 (5.66%) 
Urinary tract infection  1  18/170 (10.59%)  17/170 (10.00%)  12/171 (7.02%)  9/169 (5.33%)  13/167 (7.78%)  12/172 (6.98%)  14/170 (8.24%)  12/171 (7.02%)  0/53 (0.00%) 
Metabolism and nutrition disorders                   
Dyslipidaemia  1  8/170 (4.71%)  6/170 (3.53%)  8/171 (4.68%)  15/169 (8.88%)  11/167 (6.59%)  15/172 (8.72%)  8/170 (4.71%)  7/171 (4.09%)  2/53 (3.77%) 
Hypoglycaemia  1  4/170 (2.35%)  4/170 (2.35%)  1/171 (0.58%)  0/169 (0.00%)  1/167 (0.60%)  2/172 (1.16%)  2/170 (1.18%)  0/171 (0.00%)  3/53 (5.66%) 
Nervous system disorders                   
Dizziness  1  6/170 (3.53%)  9/170 (5.29%)  4/171 (2.34%)  5/169 (2.96%)  3/167 (1.80%)  4/172 (2.33%)  4/170 (2.35%)  7/171 (4.09%)  3/53 (5.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 800-243-0127 ext +1
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01719003     History of Changes
Other Study ID Numbers: 1276.1
2010-021375-92 ( EudraCT Number: EudraCT )
First Submitted: October 30, 2012
First Posted: November 1, 2012
Results First Submitted: November 23, 2015
Results First Posted: February 19, 2016
Last Update Posted: February 19, 2016