Trial Outcomes & Findings for Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes (NCT NCT00982644)

NCT ID: NCT00982644

Last Updated: 2017-02-09

Results Overview

Change from baseline in HbA1c after 52 weeks of treatment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1030 participants
• Primary outcome timeframe: Week 0, Week 52
• Results posted on: 2017-02-09

Participant Flow

The trial was conducted at 166 sites in 12 countries: Austria (6 sites), Belgium (5 sites), Canada (17 sites), Czech Republic (5 sites), Denmark (6 sites), Finland (6 sites), France (7 sites), Germany (16 sites), Norway (8 sites), Serbia (5 sites), Spain (9 sites) and United States (76 sites). Some subjects did not enrol in the extension period.

All subjects who completed the 52-week main trial (NN51250-3579, NCT00982644) and when found to be eligible for the extension trial, were offered to participate in the 52-week extension trial (NN1250-3643). The total duration of treatment was up to 104 weeks (52 weeks + 52 weeks).

Participant milestones

Measure	IDeg OD Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main: Week 0 to 52 (NN1250-3579) STARTED	773	257
Main: Week 0 to 52 (NN1250-3579) Full Analysis Set	773	257
Main: Week 0 to 52 (NN1250-3579) Exposed	766	257
Main: Week 0 to 52 (NN1250-3579) COMPLETED	607	197
Main: Week 0 to 52 (NN1250-3579) NOT COMPLETED	166	60
Extension: Week 53 to 104 (NN1250-3643) STARTED	551	174
Extension: Week 53 to 104 (NN1250-3643) COMPLETED	505	154
Extension: Week 53 to 104 (NN1250-3643) NOT COMPLETED	46	20

Reasons for withdrawal

Measure	IDeg OD Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main: Week 0 to 52 (NN1250-3579) Adverse Event	20	5
Main: Week 0 to 52 (NN1250-3579) Lack of Efficacy	7	2
Main: Week 0 to 52 (NN1250-3579) Protocol Violation	46	18
Main: Week 0 to 52 (NN1250-3579) Withdrawal criteria	9	5
Main: Week 0 to 52 (NN1250-3579) Unclassified	84	30
Extension: Week 53 to 104 (NN1250-3643) Adverse Event	12	5
Extension: Week 53 to 104 (NN1250-3643) Lack of Efficacy	3	1
Extension: Week 53 to 104 (NN1250-3643) Protocol Violation	2	4
Extension: Week 53 to 104 (NN1250-3643) Withdrawal criteria	6	3
Extension: Week 53 to 104 (NN1250-3643) Unclassified	23	7

Baseline Characteristics

Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	IDeg OD n=773 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.	Total n=1030 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	58.7 years STANDARD_DEVIATION 9.9 • n=7 Participants	59.1 years STANDARD_DEVIATION 9.8 • n=5 Participants
Gender Female	302 Participants n=5 Participants	90 Participants n=7 Participants	392 Participants n=5 Participants
Gender Male	471 Participants n=5 Participants	167 Participants n=7 Participants	638 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=7 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants
Fasting plasma glucose (FPG)	9.6 mmol/L STANDARD_DEVIATION 2.6 • n=5 Participants	9.7 mmol/L STANDARD_DEVIATION 2.6 • n=7 Participants	9.7 mmol/L STANDARD_DEVIATION 2.6 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 52

Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF).

Change from baseline in HbA1c after 52 weeks of treatment

Outcome measures

Measure	IDeg OD n=773 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	-1.06 percentage of glycosylated haemoglobin Standard Deviation 1.01	-1.19 percentage of glycosylated haemoglobin Standard Deviation 0.97

PRIMARY outcome

Timeframe: Week 0 to Week 104 + 7 days follow up

Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Measure	IDeg OD n=766 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	172 Episodes/100 years of patient exposure	205 Episodes/100 years of patient exposure

PRIMARY outcome

Timeframe: Week 0 to Week 104 + 7 days follow up

Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

Outcome measures

Measure	IDeg OD n=766 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	27 Episodes/100 years of patient exposure	46 Episodes/100 years of patient exposure

PRIMARY outcome

Timeframe: Week 0 to Week 104 + 7 days of follow up

Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Outcome measures

Measure	IDeg OD n=766 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Adverse event (AE)	362 Events/100 years of patient exposure	339 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Serious AE	15 Events/100 years of patient exposure	17 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Mild AE	254 Events/100 years of patient exposure	234 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Severe AE	14 Events/100 years of patient exposure	17 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Moderate AE	93 Events/100 years of patient exposure	87 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Fatal AE	0 Events/100 years of patient exposure	1 Events/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

Population: The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Measure	IDeg OD n=766 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	152 Episodes/100 years of patient exposure	185 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0, Week 104

Population: The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF.

Change from baseline in HbA1c after 104 weeks of treatment

Outcome measures

Measure	IDeg OD n=773 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment	-0.95 percentage of glycosylated haemoglobin Standard Deviation 1.04	-1.11 percentage of glycosylated haemoglobin Standard Deviation 0.99

SECONDARY outcome

Timeframe: Week 52

Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 126 subjects all 9-point SMPG values were missing.

Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.

Outcome measures

Measure	IDeg OD n=681 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=223 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52	7.7 mmol/L Standard Deviation 1.8	7.7 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Week 104

Population: The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF. For 140 subjects all 9-point SMPG values were missing.

Mean of 9-point SMPG at 104 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.

Outcome measures

Measure	IDeg OD n=666 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=224 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104	7.6 mmol/L Standard Deviation 1.9	7.6 mmol/L Standard Deviation 1.9

SECONDARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

Outcome measures

Measure	IDeg OD n=766 Participants Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 Participants Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	25 Episodes/100 years of patient exposure	39 Episodes/100 years of patient exposure

Adverse Events

IDeg OD

Serious events: 116 serious events

Other events: 463 other events

Deaths: 0 deaths

IGlar OD

Serious events: 41 serious events

Other events: 153 other events

Deaths: 0 deaths

Serious adverse events

Measure	IDeg OD n=766 participants at risk Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 participants at risk Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Cardiac disorders Acute coronary syndrome	0.52% 4/766 • Number of events 4 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Angina pectoris	0.52% 4/766 • Number of events 4 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Angina unstable	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Atrial fibrillation	0.52% 4/766 • Number of events 4 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Atrial flutter	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Cardiac failure	0.26% 2/766 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Cardiac failure congestive	0.39% 3/766 • Number of events 4 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Cardiopulmonary failure	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Congestive cardiomyopathy	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Coronary artery disease	1.3% 10/766 • Number of events 11 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Coronary artery occlusion	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Coronary artery stenosis	0.39% 3/766 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Mitral valve incompetence	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Myocardial infarction	0.39% 3/766 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Supraventricular tachycardia	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Tachyarrhythmia	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Tachycardia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Ventricular tachycardia	0.13% 1/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Ear and labyrinth disorders Vertigo	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Endocrine disorders Hyperparathyroidism primary	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Eye disorders Lens dislocation	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Abdominal pain	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Colitis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Colonic polyp	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Dyspepsia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Pancreatitis acute	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Umbilical hernia	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Chest pain	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Hernia	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Immune system disorders Hypersensitivity	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Appendicitis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Bronchopneumonia	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Cellulitis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Diverticulitis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Gastroenteritis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Gastroenteritis viral	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Influenza	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Lobar pneumonia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Pneumonia	0.52% 4/766 • Number of events 4 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Pneumonia primary atypical	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Pyelonephritis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Urosepsis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Vaginal infection	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Wound infection	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Contusion	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Fibula fracture	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Hand fracture	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Soft tissue injury	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Tooth fracture	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Arthritis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.39% 3/766 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder adenocarcinoma stage unspecified	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage I	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Aphasia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Carotid artery stenosis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Cerebral infarction	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Cerebrospinal fistula	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Cervicobrachial syndrome	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Hypoaesthesia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Ischaemic stroke	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Syncope	0.39% 3/766 • Number of events 3 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Thalamic infarction	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Psychiatric disorders Depression	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Calculus bladder	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Nephrolithiasis	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Vascular disorders Hypertensive crisis	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Vascular disorders Orthostatic hypotension	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Vascular disorders Peripheral vascular disorder	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.78% 2/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Blood and lymphatic system disorders Anaemia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Acute left ventricular failure	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Acute myocardial ischaemia	0.65% 5/766 • Number of events 5 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Cardiac arrest	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Blood and lymphatic system disorders Cardiomyopathy	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Diastolic dysfunction	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Myocardial ishaemia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Sick sinus syndrome	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Cardiac disorders Ventricular fibrillation	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Eye disorders Macular oedema	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Eye disorders Retinal haemorrhage	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Abdominal discomfort	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Enterovesical fistula	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Gastric polyp	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Inguinal hernia	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Large intestinal perforation	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Lower grastrointestinal haemorrhage	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Death	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Multiorgan failure	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Non-cardiac chest pain	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Hepatobiliary disorders Cholecystitis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Hepatobiliary disorders Cholelithiasis obstructive	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Abdominal abscess	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Diabetic foot	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Herpes zoster	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Meningitis listeria	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Pseudomembranous colitis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Pulmonary sepsis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Skin graft infection	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Urinary tract infection	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Fall	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications In-stent coronary artery restenosis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Incisional hernia	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Lower limb fracture	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Meniscus lesion	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Muscle injury	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Metabolism and nutrition disorders Diabetic foot	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Metabolism and nutrition disorders Rotator cuff syndrome	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of bladder	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of prostate	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchoalveolar carcinoma	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon carcinoma stage 3	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B cell lymphoma	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate carcinoma	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal carcinoma	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma stage 1	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebro vascular accident	0.52% 4/766 • Number of events 5 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Embolic cerebral infarction	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Hypoglycaemic unconsciousness	0.26% 2/766 • Number of events 2 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Sciatica	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Calculus urinary	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Renal cyst	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Renal failure acute	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Urethral stenosis	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Renal and urinary disorders Urinary retention	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Reproductive system and breast disorders Vaginal haemorrhage	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Nasal polyp	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Surgical and medical procedures Inguinal hernia repair	0.13% 1/766 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.00% 0/257 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Vascular disorders Hypertension	0.00% 0/766 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	0.39% 1/257 • Number of events 1 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.

Other adverse events

Measure	IDeg OD n=766 participants at risk Insulin degludec (IDeg) was given subcutaneously (s.c) once daily (OD) with the main evening meal in combination with metformin with or without DPP-IV inhibitors. IDeg was given for 52 weeks in the main period and for another 52 weeks in the extension period.	IGlar OD n=257 participants at risk Insulin glargine (IGlar) was given subcutaneously (s.c) once daily (OD), according to the local labelling in combination with metformin with or without DPP-IV inhibitors. IGlar was given for 52 weeks in the main period and for another 52 weeks in the extension period.
Gastrointestinal disorders Diarrhoea	10.8% 83/766 • Number of events 126 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	10.9% 28/257 • Number of events 36 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Vomiting	4.4% 34/766 • Number of events 44 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	6.6% 17/257 • Number of events 20 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Bronchitis	9.1% 70/766 • Number of events 99 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	7.8% 20/257 • Number of events 23 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Nasopharyngitis	23.9% 183/766 • Number of events 310 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	25.3% 65/257 • Number of events 108 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	10.2% 78/766 • Number of events 121 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	7.4% 19/257 • Number of events 33 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Back pain	9.9% 76/766 • Number of events 129 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	8.9% 23/257 • Number of events 39 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Headache	13.8% 106/766 • Number of events 192 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	11.7% 30/257 • Number of events 57 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 61/766 • Number of events 80 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.4% 14/257 • Number of events 20 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Nausea	5.4% 41/766 • Number of events 55 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	4.3% 11/257 • Number of events 17 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
General disorders Oedema peripheral	6.0% 46/766 • Number of events 55 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	4.3% 11/257 • Number of events 12 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Gastrointestinal disorders Gastroenteritis	4.4% 34/766 • Number of events 40 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.8% 15/257 • Number of events 16 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Influenza	5.7% 44/766 • Number of events 50 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.1% 13/257 • Number of events 18 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Infections and infestations Urinary tract infection	5.9% 45/766 • Number of events 64 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.4% 14/257 • Number of events 17 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 45/766 • Number of events 57 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	4.7% 12/257 • Number of events 14 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.9% 30/766 • Number of events 37 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.1% 13/257 • Number of events 14 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Musculoskeletal and connective tissue disorders Pain In Extremity	5.7% 44/766 • Number of events 53 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	4.3% 11/257 • Number of events 11 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.
Nervous system disorders Dizziness	4.0% 31/766 • Number of events 40 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.	5.4% 14/257 • Number of events 18 • Adverse events were collected in a time frame of 104 weeks + 7 days follow up. The SAS included all subjects who received at least one dose of investigational product or its comparator.

Additional Information

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Restriction type: OTHER