Trial Outcomes & Findings for 12 Weeks Treatment With 3 Different Doses of BI 10773 in Type 2 Diabetic Patients (NCT NCT00789035)

NCT ID: NCT00789035

Last Updated: 2014-06-18

Results Overview

Change of HbA1c from baseline after 12 weeks of treatment. Note, adjusted means are presented. For the placebo and empa groups, measured values presented are for the model including only these treatment groups, for the metformin group the measured values presented are for the model including only placebo and metformin groups.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 408 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2014-06-18

Participant Flow

Participant milestones

Measure	Placebo Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL Patients were to take a open-label (OL) dose of 500 mg Metformin twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Overall Study STARTED	82	81	81	82	80
Overall Study COMPLETED	76	74	80	81	74
Overall Study NOT COMPLETED	6	7	1	1	6

Reasons for withdrawal

Measure	Placebo Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL Patients were to take a open-label (OL) dose of 500 mg Metformin twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Overall Study Adverse Event	0	2	0	1	3
Overall Study Lack of Efficacy	3	0	0	0	2
Overall Study Protocol Violation	1	0	0	0	0
Overall Study Withdrawal by Subject	0	2	0	0	0
Overall Study Other reason not defined above	2	3	1	0	1

Baseline Characteristics

12 Weeks Treatment With 3 Different Doses of BI 10773 in Type 2 Diabetic Patients

Baseline characteristics by cohort

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.	Total n=406 Participants Total of all reporting groups
Age, Continuous	57.5 years STANDARD_DEVIATION 10.2 • n=5 Participants	58.4 years STANDARD_DEVIATION 9.7 • n=7 Participants	58.2 years STANDARD_DEVIATION 9.9 • n=5 Participants	56.4 years STANDARD_DEVIATION 10.3 • n=4 Participants	57.0 years STANDARD_DEVIATION 8.9 • n=21 Participants	57.5 years STANDARD_DEVIATION 9.8 • n=10 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	35 Participants n=7 Participants	41 Participants n=5 Participants	41 Participants n=4 Participants	41 Participants n=21 Participants	195 Participants n=10 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	46 Participants n=7 Participants	40 Participants n=5 Participants	41 Participants n=4 Participants	39 Participants n=21 Participants	211 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: The full analysis set (FAS) consists of all randomised patients who were treated with at least 1 dose of study drug and had a baseline measurement of the primary endpoint. Modified last observation carried forward was used as the imputation method (LOCF).

Change of HbA1c from baseline after 12 weeks of treatment.

Note, adjusted means are presented. For the placebo and empa groups, measured values presented are for the model including only these treatment groups, for the metformin group the measured values presented are for the model including only placebo and metformin groups.

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change of Glycosilated Haemoglobin A1c (HbA1c) From Baseline After 12 Weeks of Treatment	0.09 percentage of HbA1c Standard Error 0.09	-0.43 percentage of HbA1c Standard Error 0.09	-0.48 percentage of HbA1c Standard Error 0.09	-0.63 percentage of HbA1c Standard Error 0.09	-0.75 percentage of HbA1c Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (LOCF)

Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis.

Note, adjusted means are presented. For the placebo and empa groups, measured values presented are for the model including only these treatment groups, for the metformin group the measured values presented are for the model including only placebo and metformin groups.

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=80 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=80 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change of FPG From Baseline After 12 Weeks of Treatment	0.79 mg/dL Standard Error 3.54	-23.26 mg/dL Standard Error 3.59	-28.92 mg/dL Standard Error 3.59	-31.08 mg/dL Standard Error 3.59	-29.96 mg/dL Standard Error 4.02

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8 and 12

Population: FAS, classical last observation carried forward (CLOCF) was used as the imputation method.

Change of HbA1c from baseline over time. Results presented stem from a repeated measures analysis.

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change of HbA1c From Baseline Over Time Week 8	0.04 percentage of HbA1c Standard Error 0.07	-0.43 percentage of HbA1c Standard Error 0.08	-0.53 percentage of HbA1c Standard Error 0.08	-0.58 percentage of HbA1c Standard Error 0.07	-0.59 percentage of HbA1c Standard Error 0.08
Change of HbA1c From Baseline Over Time Week 12	0.07 percentage of HbA1c Standard Error 0.08	-0.47 percentage of HbA1c Standard Error 0.08	-0.53 percentage of HbA1c Standard Error 0.08	-0.66 percentage of HbA1c Standard Error 0.08	-0.78 percentage of HbA1c Standard Error 0.08
Change of HbA1c From Baseline Over Time Week 4	-0.01 percentage of HbA1c Standard Error 0.06	-0.27 percentage of HbA1c Standard Error 0.06	-0.24 percentage of HbA1c Standard Error 0.06	-0.39 percentage of HbA1c Standard Error 0.06	-0.26 percentage of HbA1c Standard Error 0.07

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS (CLOCF)

Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%).

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment	22.0 percentage of participants	33.3 percentage of participants	29.6 percentage of participants	45.1 percentage of participants	45.0 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS (CLOCF)

Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%).

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment	25.6 percentage of participants	46.9 percentage of participants	59.3 percentage of participants	59.8 percentage of participants	71.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

Results for change of FPI from baseline at week 12 based on ANCOVA.

Outcome measures

Measure	Placebo n=70 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=69 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=70 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=77 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=68 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI)	-0.95 mU/L Standard Error 0.53	-0.90 mU/L Standard Error 0.53	-1.02 mU/L Standard Error 0.53	-0.90 mU/L Standard Error 0.50	-0.01 mU/L Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

HOMA-IR (to assess insulin resistance) is defined as (FPI x FPG)/22.5. Results based on ANCOVA.

Outcome measures

Measure	Placebo n=70 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=69 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=70 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=77 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=68 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR)	-0.19 mU/L x mmol/L Standard Error 0.26	-0.85 mU/L x mmol/L Standard Error 0.27	-0.83 mU/L x mmol/L Standard Error 0.26	-0.79 mU/L x mmol/L Standard Error 0.25	-0.37 mU/L x mmol/L Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

HOMA-%B (to assess insulin beta cell function) is defined as (20 x FPI)/(FPG-3.5). Results are based on ANCOVA.

Outcome measures

Measure	Placebo n=70 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=69 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=70 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=77 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=68 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B)	-5.20 mU / mmol Standard Error 2.56	4.22 mU / mmol Standard Error 2.57	1.09 mU / mmol Standard Error 2.54	2.13 mU / mmol Standard Error 2.43	6.69 mU / mmol Standard Error 2.58

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

Results for change of body weight after 12 weeks of treatment based on ANCOVA.

Outcome measures

Measure	Placebo n=82 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=81 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=82 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 Participants Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Change of Body Weight After 12 Weeks of Treatment	-0.75 kg Standard Error 0.26	-1.81 kg Standard Error 0.26	-2.33 kg Standard Error 0.26	-2.03 kg Standard Error 0.26	-1.32 kg Standard Error 0.26

SECONDARY outcome

Timeframe: Days 28, 56 and 84

Population: All patients who received at least one dose of Empagliflozin and have some Pharmacokinetic (PK) data.

Pre-dose (within 30 minutes before dosing) trough concentrations of Empagliflozin in plasma

Outcome measures

Measure	Placebo n=70 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=77 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=77 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Trough Concentrations of Empagliflozin in Plasma Day 28 (N=67, 75, 77)	31.6 nmol/L Geometric Coefficient of Variation 158	61.7 nmol/L Geometric Coefficient of Variation 169	117 nmol/L Geometric Coefficient of Variation 154	—	—
Trough Concentrations of Empagliflozin in Plasma Day 56 (N=69, 73, 75)	20.3 nmol/L Geometric Coefficient of Variation 128	51.6 nmol/L Geometric Coefficient of Variation 190	127 nmol/L Geometric Coefficient of Variation 140	—	—
Trough Concentrations of Empagliflozin in Plasma Day 84 (N=70, 77, 75)	22.9 nmol/L Geometric Coefficient of Variation 132	55.3 nmol/L Geometric Coefficient of Variation 156	118 nmol/L Geometric Coefficient of Variation 179	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Empagliflozin 5 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Empagliflozin 10 mg qd

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Empagliflozin 25 mg qd

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Metformin OL

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=82 participants at risk Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 participants at risk Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg qd n=81 participants at risk Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg qd n=82 participants at risk Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 participants at risk Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Cardiac disorders Acute myocardial infarction	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Cardiac disorders Myocardial infarction	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Cardiac disorders Prinzmetal angina	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Gastrointestinal disorders Intestinal functional disorder	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Injury, poisoning and procedural complications Hand fracture	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days

Other adverse events

Measure	Placebo n=82 participants at risk Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 5 mg n=81 participants at risk Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg qd n=81 participants at risk Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg qd n=82 participants at risk Patients receive 25 mg Empagliflozin in tablets once daily.	Metformin OL n=80 participants at risk Patients were to take a dose of 500 mg Metformin (open-label) twice daily for the first 4 weeks. For the remaining 8 weeks, if the fasted blood glucose values were above 110 mg/dL (6.1 mmol/L), the dose was to be increased to 2 x 500 mg tablets twice daily or up to the maximum tolerated.
Gastrointestinal disorders Diarrhoea	1.2% 1/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	8.8% 7/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days
General disorders Thirst	0.00% 0/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	2.5% 2/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	6.2% 5/81 • From first drug administration until 7 days after last intake of study medication, up to 121 days	1.2% 1/82 • From first drug administration until 7 days after last intake of study medication, up to 121 days	0.00% 0/80 • From first drug administration until 7 days after last intake of study medication, up to 121 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER