Trial Outcomes & Findings for BI 10773 add-on to Metformin in Patients With Type 2 Diabetes (NCT NCT00749190)

Results Overview

Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

495 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2014-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg Patients receive 1 mg Empagliflozin in tablets 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.	Empagliflozin 50 mg Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Overall Study STARTED	71	71	71	71	70	70	71
Overall Study COMPLETED	66	66	70	66	70	65	70
Overall Study NOT COMPLETED	5	5	1	5	0	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg Patients receive 1 mg Empagliflozin in tablets 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 50 mg Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Overall Study Adverse Event	0	2	0	4	3	0
Overall Study Lack of Efficacy	3	1	1	0	1	0
Overall Study Withdrawal by Subject	2	1	0	0	1	0
Overall Study Protocol Violation	0	1	0	0	0	1
Overall Study Other reason not defined above	0	0	0	1	0	0

Baseline Characteristics

BI 10773 add-on to Metformin in Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empa 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empa 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empa 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empa 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empa 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitag n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.	Total n=495 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 8.5 • n=93 Participants	57.4 years STANDARD_DEVIATION 8.8 • n=4 Participants	59.7 years STANDARD_DEVIATION 7.3 • n=27 Participants	59.0 years STANDARD_DEVIATION 9.0 • n=483 Participants	58.7 years STANDARD_DEVIATION 8.1 • n=36 Participants	55.9 years STANDARD_DEVIATION 9.4 • n=10 Participants	57.6 years STANDARD_DEVIATION 10.1 • n=115 Participants	58.3 years STANDARD_DEVIATION 8.8 • n=40 Participants
Sex: Female, Male Female	38 Participants n=93 Participants	30 Participants n=4 Participants	42 Participants n=27 Participants	38 Participants n=483 Participants	33 Participants n=36 Participants	31 Participants n=10 Participants	33 Participants n=115 Participants	245 Participants n=40 Participants
Sex: Female, Male Male	33 Participants n=93 Participants	41 Participants n=4 Participants	29 Participants n=27 Participants	33 Participants n=483 Participants	37 Participants n=36 Participants	39 Participants n=10 Participants	38 Participants n=115 Participants	250 Participants n=40 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Full analysis set (FAS) consisting of all randomized patients who were treated with at least one dose of study drug and has a baseline measurement of the primary endpoint. The imputation method used was a modified last observation carried forward (LOCF) approach which used linear interpolation, LOCF and worst observation carried forward (WOCF).

Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change From Baseline in HbA1c After 12 Weeks of Treatment	0.15 percentage of HbA1c Standard Error 0.08	-0.09 percentage of HbA1c Standard Error 0.08	-0.23 percentage of HbA1c Standard Error 0.08	-0.56 percentage of HbA1c Standard Error 0.08	-0.55 percentage of HbA1c Standard Error 0.08	-0.49 percentage of HbA1c Standard Error 0.08	-0.45 percentage of HbA1c Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS using modified LOCF imputation method

Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.

Outcome measures

Outcome measures
Measure	Placebo n=69 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=68 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=70 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=68 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=69 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=69 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=69 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change of FPG From Baseline After 12 Weeks of Treatment	4.75 mg/dL Standard Error 3.48	-1.70 mg/dL Standard Error 3.49	-15.84 mg/dL Standard Error 3.45	-22.14 mg/dL Standard Error 3.49	-26.83 mg/dL Standard Error 3.47	-27.91 mg/dL Standard Error 3.47	-12.92 mg/dL Standard Error 4.73

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8 and 12

Population: FAS. Imputation method used was the classical LOCF (CLOCF) approach which uses always the last available value.

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

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change of HbA1c From Baseline Over Time Week 4	0.02 percentage of HbA1c Standard Error 0.06	-0.12 percentage of HbA1c Standard Error 0.06	-0.16 percentage of HbA1c Standard Error 0.06	-0.32 percentage of HbA1c Standard Error 0.06	-0.31 percentage of HbA1c Standard Error 0.06	-0.36 percentage of HbA1c Standard Error 0.06	-0.26 percentage of HbA1c Standard Error 0.06
Change of HbA1c From Baseline Over Time Week 8	0.05 percentage of HbA1c Standard Error 0.07	-0.14 percentage of HbA1c Standard Error 0.07	-0.30 percentage of HbA1c Standard Error 0.07	-0.57 percentage of HbA1c Standard Error 0.07	-0.52 percentage of HbA1c Standard Error 0.07	-0.53 percentage of HbA1c Standard Error 0.07	-0.40 percentage of HbA1c Standard Error 0.07
Change of HbA1c From Baseline Over Time Week 12	0.12 percentage of HbA1c Standard Error 0.08	-0.08 percentage of HbA1c Standard Error 0.08	-0.27 percentage of HbA1c Standard Error 0.08	-0.57 percentage of HbA1c Standard Error 0.08	-0.59 percentage of HbA1c Standard Error 0.08	-0.50 percentage of HbA1c Standard Error 0.08	-0.45 percentage of HbA1c Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%) based on logistic regression

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment	15.5 percentage of participants	23.9 percentage of participants	21.1 percentage of participants	38.0 percentage of participants	37.1 percentage of participants	35.7 percentage of participants	33.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS (CLOCF)

Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%) based on logistic regression

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment	21.1 percentage of participants	31.0 percentage of participants	40.8 percentage of participants	60.6 percentage of participants	60.0 percentage of participants	48.6 percentage of participants	53.5 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

Outcome measures
Measure	Placebo n=63 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=59 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=60 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=59 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=57 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=61 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=59 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI)	0.43 mU/L Standard Error 0.57	0.09 mU/L Standard Error 0.59	-0.84 mU/L Standard Error 0.58	-1.77 mU/L Standard Error 0.58	-0.11 mU/L Standard Error 0.59	-1.52 mU/L Standard Error 0.57	1.84 mU/L Standard Error 0.58

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

Outcome measures
Measure	Placebo n=62 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=58 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=59 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=59 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=57 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=59 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=59 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR)	0.23 mU/L x mmol/L Standard Error 0.26	-0.11 mU/L x mmol/L Standard Error 0.27	-0.60 mU/L x mmol/L Standard Error 0.26	-1.04 mU/L x mmol/L Standard Error 0.26	-0.52 mU/L x mmol/L Standard Error 0.27	-1.10 mU/L x mmol/L Standard Error 0.27	0.48 mU/L x mmol/L Standard Error 0.26

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), FPG in mg/dl. Results are based on ANCOVA.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=58 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=58 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=59 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=57 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=59 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=59 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B)	0.30 mU / mmol Standard Error 2.70	0.08 mU / mmol Standard Error 2.77	0.36 mU / mmol Standard Error 2.76	1.55 mU / mmol Standard Error 2.72	6.68 mU / mmol Standard Error 2.78	4.01 mU / mmol Standard Error 2.76	12.38 mU / mmol Standard Error 2.75

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

Outcome measures
Measure	Placebo n=71 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 Participants Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 Participants Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Change of Body Weight After 12 Weeks of Treatment	-1.16 kg Standard Error 0.31	-1.55 kg Standard Error 0.31	-2.28 kg Standard Error 0.31	-2.74 kg Standard Error 0.31	-2.56 kg Standard Error 0.31	-2.85 kg Standard Error 0.32	-0.84 kg Standard Error 0.31

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) trough concentrations of Empagliflozin in plasma, within 30 minutes of dosing.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=65 Participants Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=64 Participants Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=61 Participants Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=63 Participants Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Trough Concentrations of Empagliflozin in Plasma Day 84 (N=53, 61, 59, 57, 57)	2.87 nmol/L Geometric Coefficient of Variation 80.1	11.2 nmol/L Geometric Coefficient of Variation 69.6	23.4 nmol/L Geometric Coefficient of Variation 85.1	71.0 nmol/L Geometric Coefficient of Variation 111	112 nmol/L Geometric Coefficient of Variation 79.6	—	—
Trough Concentrations of Empagliflozin in Plasma Day 28 (N=58, 65, 62, 58, 63)	3.19 nmol/L Geometric Coefficient of Variation 88.8	13.1 nmol/L Geometric Coefficient of Variation 79.4	27.3 nmol/L Geometric Coefficient of Variation 127	92.5 nmol/L Geometric Coefficient of Variation 111	119 nmol/L Geometric Coefficient of Variation 78.7	—	—
Trough Concentrations of Empagliflozin in Plasma Day 56 (N=56, 64, 64, 61, 61)	2.93 nmol/L Geometric Coefficient of Variation 69.6	11.5 nmol/L Geometric Coefficient of Variation 63.2	23.0 nmol/L Geometric Coefficient of Variation 93.8	75.4 nmol/L Geometric Coefficient of Variation 140	119 nmol/L Geometric Coefficient of Variation 85.5	—	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Empagliflozin 1 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Empagliflozin 5 mg

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Empagliflozin 10 mg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Empagliflozin 25 mg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Empagliflozin 50 mg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Sitagliptin OL

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=71 participants at risk Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 participants at risk Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 participants at risk Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 participants at risk Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 participants at risk Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 participants at risk Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 participants at risk Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Cardiac disorders Atrial fibrillation	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Cardiac disorders Coronary artery disease	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Cardiac disorders Myocardial infarction	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Cardiac disorders Myocardial ischaemia	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Endocrine disorders Thyroid cyst	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
General disorders Chest discomfort	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
General disorders Chest pain	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Hepatobiliary disorders Cholecystitis acute	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Infections and infestations Pneumonia	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Infections and infestations Pyelonephritis	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days

Other adverse events

Other adverse events
Measure	Placebo n=71 participants at risk Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily.	Empagliflozin 1 mg n=71 participants at risk Patients receive 1 mg Empagliflozin in tablets once daily.	Empagliflozin 5 mg n=71 participants at risk Patients receive 5 mg Empagliflozin in tablets once daily.	Empagliflozin 10 mg n=71 participants at risk Patients receive 10 mg Empagliflozin in tablets once daily.	Empagliflozin 25 mg n=70 participants at risk Patients receive 25 mg Empagliflozin in tablets once daily.	Empagliflozin 50 mg n=70 participants at risk Patients receive 50 mg Empagliflozin in tablets once daily.	Sitagliptin OL n=71 participants at risk Patients receive 100 mg Sitagliptin (open-label) in tablets once daily.
Infections and infestations Urinary tract infection	2.8% 2/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	2.8% 2/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	4.2% 3/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	5.7% 4/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	2.8% 2/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days
Vascular disorders Hypertension	2.8% 2/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	1.4% 1/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	5.6% 4/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	0.00% 0/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	2.9% 2/70 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days	2.8% 2/71 • From first dose of study medication until 7 days following the last intake of study medication, up to 100 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

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