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Empagliflozin (BI 10773) in Type Two Diabetes (T2D) Patients, Open Label Extension

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ClinicalTrials.gov Identifier: NCT00881530
Recruitment Status : Completed
First Posted : April 15, 2009
Results First Posted : June 16, 2014
Last Update Posted : June 16, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: BI 10773
Drug: Metformin
Drug: Sitagliptin
Enrollment 660
Recruitment Details This was an open label extension trial of the blinded 12-week dose-finding studies NCT00789035 and NCT00749190.
Pre-assignment Details Patients from the preceding empagliflozin 10 and 25 mg groups continued to take the same doses. Patients on placebo and other empagliflozin doses were re-randomised to one of the empagliflozin treatments. Patients on metformin monotherapy or sitagliptin added-on to metformin in the preceding trials continued their open label treatments.
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description Patients receive 10 mg Empagliflozin in tablets once daily. Patients receive 25 mg Empagliflozin in tablets once daily. Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial. Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Period Title: Overall Study
Started 106 109 56 166 166 56
Completed 92 104 51 157 152 51
Not Completed 14 5 5 9 14 5
Reason Not Completed
Adverse Event             5             1             1             4             10             2
Lack of Efficacy             1             0             0             0             1             1
Not compliant with the protocol             0             0             0             0             2             0
Lost to Follow-up             0             1             1             3             1             0
Refused to continue medication             7             2             1             2             0             0
Other reason not defined above             1             1             2             0             0             2
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin Total
Hide Arm/Group Description Patients receive 10 mg Empagliflozin in tablets once daily. Patients receive 25 mg Empagliflozin in tablets once daily. Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial. Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Total of all reporting groups
Overall Number of Baseline Participants 106 109 56 166 166 56 659
Hide Baseline Analysis Population Description
Treated set including all patients treated with at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 109 participants 56 participants 166 participants 166 participants 56 participants 659 participants
58.3  (8.5) 58.5  (10.0) 56.8  (8.9) 58.4  (8.3) 59.9  (7.8) 58.3  (10.5) 58.6  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 109 participants 56 participants 166 participants 166 participants 56 participants 659 participants
Female
57
  53.8%
52
  47.7%
28
  50.0%
83
  50.0%
78
  47.0%
27
  48.2%
325
  49.3%
Male
49
  46.2%
57
  52.3%
28
  50.0%
83
  50.0%
88
  53.0%
29
  51.8%
334
  50.7%
1.Primary Outcome
Title Hypoglycaemic Events
Hide Description

Investigator defined Hypoglycaemic events. For documentation of hypoglycemic events, the following criteria were taken into consideration:

  • Asymptomatic hypoglycemia: the event was not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤70 mg/dL (≤3.9 mmol/L)
  • Documented symptomatic hypoglycemia with glucose of ≥54 mg/dL and ≤70 mg/dL (≥3.0 mmol/L and ≤3.9 mmol/L)
  • Documented symptomatic hypoglycemia with glucose of <54 mg/dL (<3.0 mmol/L): the event was accompanied by typical symptoms of hypoglycemia but in no need for external assistance
  • Severe hypoglycemic episode: the event required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions
Time Frame 78 weeks plus 1 week of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Measure Type: Number
Unit of Measure: percentage of participants
0.9 1.8 7.1 2.4 3.6 5.4
2.Primary Outcome
Title Change From Baseline to Week 78 in Lipid Parameters
Hide Description Change from baseline to week 78 in lipid parameters (Total cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL) and Triglyceride)
Time Frame Weeks 1 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 105 109 56 164 162 56
Mean (Standard Deviation)
Unit of Measure: mmol/L
Total Cholesterol -0.13  (1.17) 0.09  (0.88) -0.24  (0.77) 0.19  (0.81) 0.13  (0.75) -0.05  (0.91)
HDL 0.08  (0.11) 0.07  (0.10) 0.06  (0.10) 0.06  (0.09) 0.07  (0.10) 0.03  (0.08)
LDL (N=102, 108, 52, 161, 159, 55) -0.02  (0.83) 0.05  (0.83) -0.13  (0.74) 0.13  (0.71) 0.07  (0.69) 0.00  (0.79)
Triglyceride -0.5  (2.3) -0.0  (0.6) -0.5  (1.2) 0.1  (0.9) -0.1  (0.8) -0.2  (0.9)
3.Primary Outcome
Title Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements
Hide Description Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements. New abnormal findings or worsening of baseline conditions were reported as treatment related Adverse Events.
Time Frame 78 weeks plus 1 week of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Measure Type: Number
Unit of Measure: percentage of participants
Alanine aminotransferase increased 0.9 0.9 3.6 0.6 0.6 1.8
Aspartate aminotransferase increased 1.9 0.0 1.8 0.0 0.6 0.0
Gamma−glutamyltransferase increased 0.9 0.0 1.8 0.0 1.2 0.0
Blood alkaline phosphatase increased 0.9 0.0 0.0 0.0 0.0 0.0
Blood creatine phosphokinase increased 0.9 0.0 0.0 0.0 0.0 0.0
Granulocyte count decreased 0.9 0.0 0.0 0.0 0.0 0.0
Hepatic enzyme increased 0.0 0.9 0.0 0.6 0.0 0.0
Blood creatinine increased 0.9 0.9 0.0 0.0 0.6 0.0
Creatinine renal clearance decreased 0.0 0.0 0.0 0.6 0.0 0.0
Weight decreased 0.0 0.9 0.0 0.0 0.6 0.0
Sick sinus syndrome 0.9 0.0 0.0 0.0 0.0 0.0
Tachycardia 0.9 1.8 0.0 0.6 0.6 0.0
4.Secondary Outcome
Title Change From Baseline in HbA1c Over Time
Hide Description Baseline source: before first intake of active treatment (preceding trial or Open label extension)
Time Frame Weeks 1, 6, 18, 30, 42, 54, 66 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Mean (Standard Deviation)
Unit of Measure: percentage of HbA1c
Week 6 (N=104, 108, 55, 162, 163, 54) -0.40  (0.77) -0.57  (0.81) -1.03  (0.76) -0.36  (0.67) -0.55  (0.60) -0.75  (0.80)
Week 18 (N=93, 105, 53, 149, 157, 48) -0.58  (0.75) -0.72  (0.88) -0.92  (0.91) -0.51  (0.68) -0.70  (0.68) -0.79  (0.84)
Week 30 (N=93, 99, 50, 140, 151, 45) -0.47  (0.85) -0.61  (0.90) -0.95  (0.82) -0.58  (0.69) -0.76  (0.70) -0.68  (0.82)
Week 42 (N=85, 93, 46, 132, 140, 44) -0.59  (0.87) -0.74  (0.98) -1.10  (0.80) -0.65  (0.72) -0.79  (0.76) -0.51  (1.03)
Week 54 (N=78, 85, 44, 128, 136, 41) -0.66  (0.83) -0.71  (0.87) -1.13  (0.89) -0.62  (0.76) -0.75  (0.73) -0.79  (0.79)
Week 66 (N=80, 87, 43, 120, 127, 39) -0.55  (0.80) -0.71  (1.01) -1.04  (0.79) -0.59  (0.79) -0.73  (0.77) -0.78  (0.90)
Week 78 (N=72, 84, 42, 115, 121, 38) -0.50  (0.77) -0.55  (0.90) -0.80  (0.88) -0.56  (0.80) -0.71  (0.81) -0.66  (0.99)
5.Secondary Outcome
Title Occurence of a Treat-to-target Response (HbA1c < 7.0%)
Hide Description Occurence of a treat-to-target response, defined as HbA1c < 7.0% over time
Time Frame Weeks 1, 6, 18, 30, 42, 54, 66 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Measure Type: Number
Unit of Measure: percentage of participants
Week 6 (N=104, 108, 55, 162, 163, 54) 26.9 25.0 45.5 24.1 25.2 35.2
Week 18 (N=93, 105, 53, 149, 157, 48) 33.3 33.3 45.3 31.5 37.6 35.4
Week 30 (N=93, 99, 50, 140, 151, 45) 34.4 29.3 42.0 28.6 45.7 28.9
Week 42 (N=85, 93, 46, 132, 140, 44) 41.2 40.9 52.2 39.4 47.1 25.0
Week 54 (N=78, 85, 44, 128, 136, 41) 43.6 32.9 56.8 35.9 47.8 29.3
Week 66 (N=80, 87, 43, 120, 127, 39) 31.3 39.1 44.2 35.8 48.0 38.5
Week 78 (N=72, 84, 42, 115, 121, 38) 31.9 32.1 31.0 27.0 44.6 36.8
6.Secondary Outcome
Title Occurrence of a Treat-to-target Response (HbA1c < 6.5%)
Hide Description Occurrence of a Treat-to-target Response, defined as HbA1c < 6.5% over time
Time Frame Weeks 1, 6, 18, 30, 42, 54, 66 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Measure Type: Number
Unit of Measure: percentage of participants
Week 6 (N=104, 108, 55, 162, 163, 54) 3.8 11.1 16.4 6.2 6.7 11.1
Week 18 (N=93, 105, 53, 149, 157, 48) 11.8 12.4 13.2 4.7 5.1 12.5
Week 30 (N=93, 99, 50, 140, 151, 45) 8.6 10.1 14.0 8.6 10.6 4.4
Week 42 (N=85, 93, 46, 132, 140, 44) 11.8 10.8 21.7 10.6 21.4 9.1
Week 54 (N=78, 85, 44, 128, 136, 41) 11.5 5.9 18.2 10.9 15.4 9.8
Week 66 (N=80, 87, 43, 120, 127, 39) 10.0 11.5 14.0 8.3 12.6 15.4
Week 78 (N=72, 84, 42, 115, 121, 38) 6.9 8.3 9.5 10.4 13.2 18.4
7.Secondary Outcome
Title Occurrence of a Relative Efficacy Response
Hide Description Occurrence of a Relative Efficacy Response (HbA1c Lowered by at least >=0.5% over time)
Time Frame Weeks 1, 6, 18, 30, 42, 54, 66 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Measure Type: Number
Unit of Measure: percentage of participants
Week 6 (N=104, 108, 55, 162, 163, 54) 42.3 50.9 80.0 41.4 56.4 63.0
Week 18 (N=93, 105, 53, 149, 157, 48) 51.6 61.9 77.4 53.7 61.8 66.7
Week 30 (N=93, 99, 50, 140, 151, 45) 50.5 55.6 78.0 55.0 63.6 68.9
Week 42 (N=85, 93, 46, 132, 140, 44) 58.8 60.2 82.6 62.1 66.4 54.5
Week 54 (N=78, 85, 44, 128, 136, 41) 62.8 58.8 81.8 59.4 65.4 58.5
Week 66 (N=80, 87, 43, 120, 127, 39) 53.8 56.3 76.7 55.0 64.6 66.7
Week 78 (N=72, 84, 42, 115, 121, 38) 50.0 50.0 66.7 56.5 64.5 60.5
8.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) Over Time
Hide Description Baseline source: before first intake of active treatment (preceding trial or Open label extension)
Time Frame Weeks 1, 6, 18, 30, 42, 54, 66 and 78
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description:
Patients receive 10 mg Empagliflozin in tablets once daily.
Patients receive 25 mg Empagliflozin in tablets once daily.
Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.
Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Overall Number of Participants Analyzed 106 109 56 166 166 56
Mean (Standard Deviation)
Unit of Measure: mg/dL
Week 6 (N=102, 108, 55, 156, 160, 53) -30.6  (42.5) -35.8  (39.6) -29.9  (40.0) -25.7  (35.2) -36.7  (36.3) -32.6  (42.4)
Week 18 (N=94, 103, 51, 144, 153, 45) -35.5  (37.9) -33.7  (42.0) -30.4  (40.3) -30.6  (31.6) -37.6  (35.8) -16.7  (44.0)
Week 30 (N=92, 101, 51, 133, 147, 43) -32.3  (41.4) -35.0  (39.6) -28.5  (28.9) -29.9  (34.9) -37.9  (38.6) -25.6  (38.6)
Week 42 (N=85, 93, 46, 126, 140, 42) -35.8  (39.1) -31.3  (41.4) -31.0  (35.6) -30.8  (36.4) -36.8  (34.1) -18.5  (43.1)
Week 54 (N=80, 88, 44, 124, 134, 39) -32.1  (37.2) -31.0  (37.8) -31.8  (35.9) -28.2  (33.7) -36.8  (32.5) -29.4  (35.4)
Week 66 (N=80, 86, 43, 116, 125, 38) -28.0  (41.4) -28.6  (42.6) -26.4  (35.7) -21.7  (36.2) -29.6  (36.4) -32.5  (46.9)
Week 78 (N=72, 84, 43, 112, 121, 36) -27.9  (33.1) -25.4  (40.9) -22.9  (39.7) -24.7  (41.5) -31.9  (36.5) -25.7  (48.9)
Time Frame From drug administration until 7 days after the last intake of study drug, up to 582 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Hide Arm/Group Description Patients receive 10 mg Empagliflozin in tablets once daily. Patients receive 25 mg Empagliflozin in tablets once daily. Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial. Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study. Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
All-Cause Mortality
Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
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 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/106 (9.43%)   7/109 (6.42%)   3/56 (5.36%)   10/166 (6.02%)   13/166 (7.83%)   9/56 (16.07%) 
Blood and lymphatic system disorders             
Anaemia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Cardiac disorders             
Angina pectoris  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Angina unstable  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  1/166 (0.60%)  1/56 (1.79%) 
Atrial fibrillation  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Myocardial infarction  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Palpitations  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Coronary artery disease  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Myocardial ischaemia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Ear and labyrinth disorders             
Vertigo  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Endocrine disorders             
Goitre  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Thyroid cyst  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Eye disorders             
Visual acuity reduced  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Gastrointestinal disorders             
Colonic polyp  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Abdominal hernia  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Anal fistula  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Gingival cyst  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Inguinal hernia  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Lumbar hernia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
General disorders             
Death  1  0/106 (0.00%)  0/109 (0.00%)  1/56 (1.79%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Non-cardiac chest pain  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Pyrexia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Hepatobiliary disorders             
Cholecystitis acute  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  2/56 (3.57%) 
Cholelithiasis  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  1/56 (1.79%) 
Bile duct obstruction  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Cholecystitis  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Infections and infestations             
Cellulitis  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Anal abscess  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Gastroenteritis  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Post procedural infection  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Pneumonia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Injury, poisoning and procedural complications             
Traumatic fracture  1  0/106 (0.00%)  0/109 (0.00%)  1/56 (1.79%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Fall  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Fibula fracture  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Ligament rupture  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Post procedural haematuria  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Vascular graft occlusion  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Wrist fracture  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Concussion  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Burns second degree  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Meniscus lesion  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Post procedural haematoma  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Metabolism and nutrition disorders             
Hyperglycaemia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  2/56 (3.57%) 
Musculoskeletal and connective tissue disorders             
Spinal osteoarthritis  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Osteoarthritis  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  1/166 (0.60%)  0/56 (0.00%) 
Rotator cuff syndrome  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  1/166 (0.60%)  0/56 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Breast cancer  1  0/106 (0.00%)  0/109 (0.00%)  1/56 (1.79%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Cervix carcinoma recurrent  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Refractory cytopenia with multilineage dysplasia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Transitional cell carcinoma  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Bile duct cancer  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Prostate cancer  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Chronic lymphocytic leukaemia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Nervous system disorders             
Cerebral infarction  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  2/56 (3.57%) 
Aphasia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Hemiplegia  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Ischaemic stroke  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  1/56 (1.79%) 
Transient ischaemic attack  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  2/166 (1.20%)  0/56 (0.00%) 
Cerebrovascular accident  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Carotid artery stenosis  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  1/166 (0.60%)  0/56 (0.00%) 
Renal and urinary disorders             
Urinary retention  1  0/106 (0.00%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Reproductive system and breast disorders             
Benign prostatic hyperplasia  1  2/106 (1.89%)  1/109 (0.92%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Acute respiratory failure  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  1/56 (1.79%) 
Surgical and medical procedures             
Hysterectomy  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Abortion induced  1  0/106 (0.00%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Vascular disorders             
Hypertension  1  1/106 (0.94%)  0/109 (0.00%)  0/56 (0.00%)  0/166 (0.00%)  0/166 (0.00%)  0/56 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empagliflozin 10 mg Empagliflozin 25 mg Metformin Empagliflozin 10 mg + Metformin Empagliflozin 25 mg + Metformin Sitaglipin + Metformin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/106 (32.08%)   46/109 (42.20%)   27/56 (48.21%)   74/166 (44.58%)   79/166 (47.59%)   26/56 (46.43%) 
Gastrointestinal disorders             
Nausea  1  2/106 (1.89%)  2/109 (1.83%)  3/56 (5.36%)  6/166 (3.61%)  6/166 (3.61%)  4/56 (7.14%) 
Diarrhoea  1  2/106 (1.89%)  3/109 (2.75%)  3/56 (5.36%)  3/166 (1.81%)  4/166 (2.41%)  1/56 (1.79%) 
General disorders             
Chest pain  1  2/106 (1.89%)  0/109 (0.00%)  3/56 (5.36%)  2/166 (1.20%)  0/166 (0.00%)  1/56 (1.79%) 
Fatigue  1  0/106 (0.00%)  1/109 (0.92%)  1/56 (1.79%)  1/166 (0.60%)  1/166 (0.60%)  3/56 (5.36%) 
Infections and infestations             
Nasopharyngitis  1  10/106 (9.43%)  8/109 (7.34%)  9/56 (16.07%)  12/166 (7.23%)  15/166 (9.04%)  5/56 (8.93%) 
Urinary tract infection  1  3/106 (2.83%)  4/109 (3.67%)  1/56 (1.79%)  12/166 (7.23%)  18/166 (10.84%)  5/56 (8.93%) 
Bronchitis  1  2/106 (1.89%)  3/109 (2.75%)  2/56 (3.57%)  2/166 (1.20%)  8/166 (4.82%)  6/56 (10.71%) 
Upper respiratory tract infection  1  5/106 (4.72%)  8/109 (7.34%)  1/56 (1.79%)  3/166 (1.81%)  2/166 (1.20%)  1/56 (1.79%) 
Viral infection  1  0/106 (0.00%)  7/109 (6.42%)  1/56 (1.79%)  1/166 (0.60%)  0/166 (0.00%)  0/56 (0.00%) 
Metabolism and nutrition disorders             
Hyperglycaemia  1  12/106 (11.32%)  16/109 (14.68%)  8/56 (14.29%)  36/166 (21.69%)  25/166 (15.06%)  9/56 (16.07%) 
Hypoglycaemia  1  1/106 (0.94%)  2/109 (1.83%)  4/56 (7.14%)  4/166 (2.41%)  6/166 (3.61%)  3/56 (5.36%) 
Nervous system disorders             
Headache  1  1/106 (0.94%)  7/109 (6.42%)  4/56 (7.14%)  6/166 (3.61%)  7/166 (4.22%)  0/56 (0.00%) 
Reproductive system and breast disorders             
Benign prostatic hyperplasia  1  1/106 (0.94%)  3/109 (2.75%)  0/56 (0.00%)  1/166 (0.60%)  0/166 (0.00%)  3/56 (5.36%) 
Vascular disorders             
Hypertension  1  4/106 (3.77%)  3/109 (2.75%)  4/56 (7.14%)  5/166 (3.01%)  2/166 (1.20%)  4/56 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 14.0
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: NCT00881530     History of Changes
Other Study ID Numbers: 1245.24
2008-007938-21 ( EudraCT Number: EudraCT )
First Submitted: April 14, 2009
First Posted: April 15, 2009
Results First Submitted: May 16, 2014
Results First Posted: June 16, 2014
Last Update Posted: June 16, 2014