Trial Outcomes & Findings for Safety and Efficacy of BI 10773 as add-on to Insulin Regimen in Patients With Type 2 Diabetes Mellitus (NCT NCT01306214)

NCT ID: NCT01306214

Last Updated: 2014-06-17

Results Overview

The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 566 participants
• Primary outcome timeframe: Baseline and 18 weeks
• Results posted on: 2014-06-17

Participant Flow

Participant milestones

Measure	Placebo Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Study STARTED	189	187	190
Overall Study COMPLETED	161	159	168
Overall Study NOT COMPLETED	28	28	22

Reasons for withdrawal

Measure	Placebo Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Overall Study Death	0	0	1
Overall Study Lost to Follow-up	3	5	4
Overall Study Withdrawal by Subject	24	22	16
Overall Study Not treated	1	1	1

Baseline Characteristics

Safety and Efficacy of BI 10773 as add-on to Insulin Regimen in Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Placebo n=188 Participants Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=186 Participants Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=189 Participants Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily	Total n=563 Participants Total of all reporting groups
Age, Continuous	55.3 years STANDARD_DEVIATION 10.1 • n=5 Participants	56.7 years STANDARD_DEVIATION 8.7 • n=7 Participants	58.0 years STANDARD_DEVIATION 9.4 • n=5 Participants	56.7 years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	89 Participants n=7 Participants	105 Participants n=5 Participants	307 Participants n=4 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	97 Participants n=7 Participants	84 Participants n=5 Participants	256 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 18 weeks

Population: The analysis was conducted on the full analysis set (FAS) of patients. Values after start of antidiabetic rescue therapy (week 18 definition) were set to missing and last observation carried forward (LOCF-18) was used for imputation of missing values.

The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment.

Outcome measures

Measure	Placebo n=188 Participants Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=186 Participants Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=189 Participants Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Change From Baseline in HbA1c After 18 Weeks of Treatment	-0.50 percentage of HbA1c Standard Error 0.05	-0.94 percentage of HbA1c Standard Error 0.05	-1.02 percentage of HbA1c Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: Per Protocol Set-patients in FAS without important protocol violations leading to exclusion, completed minimum treatment of 357 days and did not prematurely discontinue. Values after start of antidiabetic rescue therapy (week 52 definition) were set to missing and last observation carried forward (LOCF-52) was used for imputation of missing values.

The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment

Outcome measures

Measure	Placebo n=115 Participants Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=118 Participants Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=117 Participants Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Change From Baseline in Insulin Dose After 52 Weeks of Treatment	10.16 IU/day Standard Error 2.16	1.33 IU/day Standard Error 2.13	-1.06 IU/day Standard Error 2.14

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)

The secondary endpoint was the change from baseline in body weight after 52 weeks of treatment

Outcome measures

Measure	Placebo n=115 Participants Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=119 Participants Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=118 Participants Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Change From Baseline in Body Weight After 52 Weeks of Treatment	0.44 kg Standard Error 0.36	-1.95 kg Standard Error 0.36	-2.04 kg Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)

The secondary endpoint was the change from baseline in HbA1c after 52 weeks of treatment

Outcome measures

Measure	Placebo n=115 Participants Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=119 Participants Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=118 Participants Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Change From Baseline in HbA1c After 52 Weeks of Treatment	-0.81 percentage of HbA1c Standard Error 0.08	-1.18 percentage of HbA1c Standard Error 0.08	-1.27 percentage of HbA1c Standard Error 0.08

Adverse Events

Placebo

Serious events: 22 serious events

Other events: 146 other events

Deaths: 0 deaths

Empagliflozin 10 mg

Serious events: 20 serious events

Other events: 135 other events

Deaths: 0 deaths

Empagliflozin 25 mg

Serious events: 22 serious events

Other events: 140 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=188 participants at risk Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=186 participants at risk Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=189 participants at risk Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Infections and infestations Pneumonia	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	1.6% 3/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Anal abscess	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Appendicitis	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Diabetic gangrene	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Gastrointestinal infection	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Lobar pneumonia	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Sepsis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Subcutaneous abscess	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Urinary tract infection	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ependymoma	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Blood and lymphatic system disorders Anaemia	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Immune system disorders Sarcoidosis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Psychiatric disorders Depression	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Carpal tunnel syndrome	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Cerebrovascular accident	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Cervicobrachial syndrome	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Convulsion	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Grand mal convulsion	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Migraine	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Radiculitis	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Syncope	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Eye disorders Amaurosis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Eye disorders Angle closure glaucoma	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Eye disorders Pterygium	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Ear and labyrinth disorders Vertigo	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	1.1% 2/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Ear and labyrinth disorders Vertigo positional	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Coronary artery disease	1.1% 2/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Acute myocardial infarction	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Angina pectoris	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Bundle branch block right	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Cardiac failure	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Cardiac failure congestive	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Cor pulmonale	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Supraventricular tachycardia	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Cardiac disorders Tachycardia	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Hypertensive emergency	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Orthostatic hypotension	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Peripheral artery stenosis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Thrombophlebitis migrans	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Venous thrombosis	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Respiratory, thoracic and mediastinal disorders Asthma	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Abdominal pain	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	1.1% 2/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Diarrhoea	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Gastric ulcer	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Umbilical hernia	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Skin and subcutaneous tissue disorders Skin ulcer	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Neuropathic arthropathy	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Renal and urinary disorders Acute prerenal failure	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Renal and urinary disorders Renal colic	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Renal and urinary disorders Renal failure acute	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Renal and urinary disorders Renal impairment	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Injury, poisoning and procedural complications Concussion	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Injury, poisoning and procedural complications Humerus fracture	0.53% 1/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Injury, poisoning and procedural complications Wound	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Surgical and medical procedures Vitrectomy	0.00% 0/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.54% 1/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.00% 0/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.

Other adverse events

Measure	Placebo n=188 participants at risk Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 10 mg n=186 participants at risk Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	Empagliflozin 25 mg n=189 participants at risk Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
Infections and infestations Nasopharyngitis	21.3% 40/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	18.3% 34/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	14.3% 27/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Urinary tract infection	12.2% 23/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	12.9% 24/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	12.7% 24/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Influenza	6.4% 12/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	3.8% 7/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	7.4% 14/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Bronchitis	6.4% 12/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	5.4% 10/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	4.2% 8/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Infections and infestations Gastroenteritis	5.3% 10/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	4.3% 8/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	0.53% 1/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Hypoglycaemia	59.0% 111/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	52.2% 97/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	58.2% 110/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Metabolism and nutrition disorders Hyperglycaemia	7.4% 14/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	3.2% 6/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	3.7% 7/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Dizziness	1.1% 2/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	2.7% 5/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	6.9% 13/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Nervous system disorders Headache	4.8% 9/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	4.3% 8/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	5.8% 11/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Vascular disorders Hypertension	5.3% 10/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	4.8% 9/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	3.7% 7/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Gastrointestinal disorders Diarrhoea	9.0% 17/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	6.5% 12/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	9.0% 17/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 10/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	9.7% 18/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	5.8% 11/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.
Musculoskeletal and connective tissue disorders Back pain	7.4% 14/188 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	6.5% 12/186 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.	7.9% 15/189 • Up to 52 weeks An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. At each visit adverse events were recorded on a cumulative case report form.

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