Trial Outcomes & Findings for To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c (NCT NCT00294723)

NCT ID: NCT00294723

Last Updated: 2017-03-07

Results Overview

Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 746 participants
• Primary outcome timeframe: week 0, week 52
• Results posted on: 2017-03-07

Participant Flow

A total of 138 centres in two countries: United States of America (USA) (126) and Mexico (12).

Subjects with type 2 diabetes treated with diet/exercise or OAD (Oral Anti-Diabetic Drug) monotherapy for at least 2 months were eligible. One subject randomised to the liraglutide 1.8 mg group was withdrawn from the study prior to dosing due to protocol non compliance, subject was not included in the intent-to-treat (ITT) or safety analysis sets.

Participant milestones

Measure	Lira 1.8 Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Lira 1.2 Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Glimepiride Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Double-Blind Period 52 Weeks STARTED	247	251	248
Double-Blind Period 52 Weeks Exposed to Study Drug	246	251	248
Double-Blind Period 52 Weeks COMPLETED	173	162	152
Double-Blind Period 52 Weeks NOT COMPLETED	74	89	96
Open-Label Extension 52 Weeks STARTED	154	149	137
Open-Label Extension 52 Weeks COMPLETED	114	110	97
Open-Label Extension 52 Weeks NOT COMPLETED	40	39	40
Additional Open-Label Extension 91 Weeks STARTED	62	53	28
Additional Open-Label Extension 91 Weeks COMPLETED	34	32	8
Additional Open-Label Extension 91 Weeks NOT COMPLETED	28	21	20

Reasons for withdrawal

Measure	Lira 1.8 Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Lira 1.2 Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Glimepiride Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Double-Blind Period 52 Weeks Adverse Event	18	25	15
Double-Blind Period 52 Weeks Lack of Efficacy	9	15	25
Double-Blind Period 52 Weeks Protocol Violation	11	11	5
Double-Blind Period 52 Weeks Not specified in study report	36	38	51
Open-Label Extension 52 Weeks Adverse Event	5	5	2
Open-Label Extension 52 Weeks Lack of Efficacy	12	15	21
Open-Label Extension 52 Weeks Protocol Violation	4	3	3
Open-Label Extension 52 Weeks Not specified in study report	19	16	14
Additional Open-Label Extension 91 Weeks Adverse Event	1	1	0
Additional Open-Label Extension 91 Weeks Lack of Efficacy	24	14	16
Additional Open-Label Extension 91 Weeks Protocol Violation	1	1	1
Additional Open-Label Extension 91 Weeks Not specified in study report	2	5	3

Baseline Characteristics

To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c

Baseline characteristics by cohort

Measure	Lira 1.8 n=247 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Lira 1.2 n=251 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=248 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)	Total n=746 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	222 Participants n=5 Participants	208 Participants n=7 Participants	208 Participants n=5 Participants	638 Participants n=4 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	43 Participants n=7 Participants	40 Participants n=5 Participants	108 Participants n=4 Participants
Age, Continuous	52.0 years STANDARD_DEVIATION 10.8 • n=5 Participants	53.7 years STANDARD_DEVIATION 11.0 • n=7 Participants	53.4 years STANDARD_DEVIATION 10.9 • n=5 Participants	53.0 years STANDARD_DEVIATION 10.9 • n=4 Participants
Sex: Female, Male Female	126 Participants n=5 Participants	134 Participants n=7 Participants	115 Participants n=5 Participants	375 Participants n=4 Participants
Sex: Female, Male Male	121 Participants n=5 Participants	117 Participants n=7 Participants	133 Participants n=5 Participants	371 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	87 Participants n=5 Participants	81 Participants n=7 Participants	93 Participants n=5 Participants	261 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	160 Participants n=5 Participants	170 Participants n=7 Participants	155 Participants n=5 Participants	485 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	30 Participants n=5 Participants	34 Participants n=7 Participants	30 Participants n=5 Participants	94 Participants n=4 Participants
Race (NIH/OMB) White	186 Participants n=5 Participants	200 Participants n=7 Participants	192 Participants n=5 Participants	578 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants	46 Participants n=4 Participants
Region of Enrollment Mexico	52 participants n=5 Participants	53 participants n=7 Participants	66 participants n=5 Participants	171 participants n=4 Participants
Region of Enrollment United States	195 participants n=5 Participants	198 participants n=7 Participants	182 participants n=5 Participants	575 participants n=4 Participants
Previous anti-diabetic treatment Diet/Exercise	87 participants n=5 Participants	91 participants n=7 Participants	94 participants n=5 Participants	272 participants n=4 Participants
Previous anti-diabetic treatment Monotherapy	160 participants n=5 Participants	160 participants n=7 Participants	154 participants n=5 Participants	474 participants n=4 Participants
Body Mass Index (BMI)	32.8 kg/m^2 STANDARD_DEVIATION 6.3 • n=5 Participants	33.2 kg/m^2 STANDARD_DEVIATION 5.6 • n=7 Participants	33.2 kg/m^2 STANDARD_DEVIATION 5.6 • n=5 Participants	33.1 kg/m^2 STANDARD_DEVIATION 5.8 • n=4 Participants
Duration of diabetes	5.3 years STANDARD_DEVIATION 5.1 • n=5 Participants	5.2 years STANDARD_DEVIATION 5.5 • n=7 Participants	5.6 years STANDARD_DEVIATION 5.1 • n=5 Participants	5.4 years STANDARD_DEVIATION 5.3 • n=4 Participants
HbA1c (Glycosylated Haemoglobin A1c)	8.3 percentage of total haemoglobin STANDARD_DEVIATION 1.1 • n=5 Participants	8.3 percentage of total haemoglobin STANDARD_DEVIATION 1.0 • n=7 Participants	8.4 percentage of total haemoglobin STANDARD_DEVIATION 1.2 • n=5 Participants	8.3 percentage of total haemoglobin STANDARD_DEVIATION 1.1 • n=4 Participants

PRIMARY outcome

Timeframe: week 0, week 52

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)

Outcome measures

Measure	Lira 1.2 n=236 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=234 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=241 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52	-0.84 percentage point of total HbA1c Standard Error 0.08	-1.14 percentage point of total HbA1c Standard Error 0.08	-0.51 percentage point of total HbA1c Standard Error 0.08

PRIMARY outcome

Timeframe: week 0, week 104

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension)

Outcome measures

Measure	Lira 1.2 n=236 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=234 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=241 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104	-0.59 percentage point of total HbA1c Standard Error 0.09	-0.88 percentage point of total HbA1c Standard Error 0.09	-0.28 percentage point of total HbA1c Standard Error 0.09

PRIMARY outcome

Timeframe: week 0, week 156

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks

Outcome measures

Measure	Lira 1.2 n=236 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=234 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=241 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156	-0.44 percentage point of total HbA1c Standard Error 0.09	-0.71 percentage point of total HbA1c Standard Error 0.09	-0.16 percentage point of total HbA1c Standard Error 0.08

SECONDARY outcome

Timeframe: week 0, week 52

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)

Outcome measures

Measure	Lira 1.2 n=245 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=240 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=248 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Body Weight at Week 52	-2.05 kg Standard Error 0.28	-2.45 kg Standard Error 0.28	1.12 kg Standard Error 0.27

SECONDARY outcome

Timeframe: week 0, week 104

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)

Outcome measures

Measure	Lira 1.2 n=245 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=240 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=248 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Body Weight at Week 104	-1.89 kg Standard Error 0.31	-2.70 kg Standard Error 0.32	0.95 kg Standard Error 0.30

SECONDARY outcome

Timeframe: week 0, week 156

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in body weight from baseline (week 0) to 156 weeks

Outcome measures

Measure	Lira 1.2 n=245 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=240 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=248 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Body Weight at Week 156	-1.68 kg Standard Error 0.32	-2.43 kg Standard Error 0.32	1.05 kg Standard Error 0.31

SECONDARY outcome

Timeframe: week 0, week 52

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)

Outcome measures

Measure	Lira 1.2 n=234 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=230 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=242 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Fasting Plasma Glucose at Week 52	-15.21 mg/dL Standard Error 3.50	-25.57 mg/dL Standard Error 3.50	-5.29 mg/dL Standard Error 3.33

SECONDARY outcome

Timeframe: week 0, week 104

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)

Outcome measures

Measure	Lira 1.2 n=234 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=230 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=242 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Fasting Plasma Glucose at Week 104	-9.36 mg/dL Standard Error 3.85	-15.82 mg/dL Standard Error 3.85	1.97 mg/dL Standard Error 3.66

SECONDARY outcome

Timeframe: week 0, week 156

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks

Outcome measures

Measure	Lira 1.2 n=234 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=230 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=242 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Fasting Plasma Glucose at Week 156	-5.45 mg/dL Standard Error 3.8	-12.06 mg/dL Standard Error 3.8	4.57 mg/dL Standard Error 3.62

SECONDARY outcome

Timeframe: week 0, week 52

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=182 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52	-30.8 mg/dL Standard Error 3.40	-37.4 mg/dL Standard Error 3.37	-24.5 mg/dL Standard Error 3.32

SECONDARY outcome

Timeframe: week 0, week 104

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=183 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104	-27.34 mg/dL Standard Error 3.68	-37.15 mg/dL Standard Error 3.64	-24.85 mg/dL Standard Error 3.58

SECONDARY outcome

Timeframe: week 0, week 156

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=183 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156	-25.68 mg/dL Standard Error 3.69	-34.83 mg/dL Standard Error 3.65	-23.84 mg/dL Standard Error 3.59

SECONDARY outcome

Timeframe: week 0, week 52

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=182 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52	-8.4 mg/dL Standard Error 2.10	-9.6 mg/dL Standard Error 2.07	-5.6 mg/dL Standard Error 2.04

SECONDARY outcome

Timeframe: week 0, week 104

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=183 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104	-8.28 mg/dL Standard Error 2.14	-11.76 mg/dL Standard Error 2.11	-7.95 mg/dL Standard Error 2.08

SECONDARY outcome

Timeframe: week 0, week 156

Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

Outcome measures

Measure	Lira 1.2 n=187 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=191 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=183 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156	-7.53 mg/dL Standard Error 2.14	-11.01 mg/dL Standard Error 2.11	-7.97 mg/dL Standard Error 2.07

SECONDARY outcome

Timeframe: weeks 0-104

Population: Full safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

Outcome measures

Measure	Lira 1.2 n=251 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=246 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=248 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Hypoglycaemic Episodes Major	0 episodes	1 episodes	0 episodes
Hypoglycaemic Episodes Minor	68 episodes	71 episodes	533 episodes
Hypoglycaemic Episodes Symptoms only	133 episodes	87 episodes	405 episodes

SECONDARY outcome

Timeframe: weeks 104-195

Population: Safety analysis set is all subjects who entered the year 3 extension at week 104.

Total number of hypoglycaemic episodes occuring from week 104 to end of trial (week 195). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

Outcome measures

Measure	Lira 1.2 n=53 Participants Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)	Lira 1.8 n=62 Participants Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)	Glimepiride n=28 Participants Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)
Hypoglycaemic Episodes Symptoms only	1 episodes	3 episodes	4 episodes
Hypoglycaemic Episodes Major	0 episodes	0 episodes	1 episodes
Hypoglycaemic Episodes Minor	3 episodes	13 episodes	34 episodes

Adverse Events

Lira 1.8 (Weeks 0-104)

Serious events: 22 serious events

Other events: 183 other events

Deaths: 0 deaths

Lira 1.2 (Weeks 0-104)

Serious events: 23 serious events

Other events: 181 other events

Deaths: 0 deaths

Glimepiride (Weeks 0-104)

Serious events: 20 serious events

Other events: 148 other events

Deaths: 0 deaths

Lira 1.8 (Weeks 104-195)

Serious events: 5 serious events

Other events: 40 other events

Deaths: 0 deaths

Lira 1.2 (Weeks 104-195)

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Glimepiride (Weeks 104-195)

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lira 1.8 (Weeks 0-104) n=246 participants at risk Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension period (weeks 52-104)	Lira 1.2 (Weeks 0-104) n=251 participants at risk Liraglutide 1.2 mg once daily + glimepiride placebo 8mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension period (weeks 52-104)	Glimepiride (Weeks 0-104) n=248 participants at risk Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension period (weeks 52-104)	Lira 1.8 (Weeks 104-195) n=62 participants at risk Open-label liraglutide 1.8 mg once daily in the additional extension period (weeks 104-195)	Lira 1.2 (Weeks 104-195) n=53 participants at risk Open-label liraglutide 1.2 mg once daily in the additional extension period (weeks 104-195)	Glimepiride (Weeks 104-195) n=28 participants at risk Open-label glimepiride 8 mg once daily in the additional extension period (weeks 104-195)
Blood and lymphatic system disorders Anaemia	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Angina Pectoris	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.81% 2/248 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Angina Unstable	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Atrial Fibrillation	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Coronary Artery Disease	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Ischaemic Cardiomyopathy	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Myocardial Infarction	0.81% 2/246 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Myocardial Ischaemia	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.81% 2/248 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Supraventricular Tachycardia	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Cardiac disorders Tachycardia	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Endocrine disorders Adrenocortical Insufficiency Acute	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.80% 2/251 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Endocrine disorders Thyroid Disorder	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Eye disorders Retinal Detachment	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Eye disorders Vision Blurred	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Appendicitis Perforated	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Crohn's Disease	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Diarrhoea	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Diverticulum Oesophageal	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Haemorrhoids	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Ileus	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Oedematous Pancreatitis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Pancreatitis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Pancreatitis Acute	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
General disorders Chest Pain	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Hepatobiliary disorders Cholecystitis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Hepatobiliary disorders Cholelithiasis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Abscess Limb	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Cellulitis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Clostridial Infection	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Fungaemia	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Gastroenteritis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Upper Respiratory Tract Infection	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Urinary Tract Infection	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Viral Infection	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Lower Limb Fracture	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Skin Laceration	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Tendon Injury	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Traumatic Coma	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Injury, poisoning and procedural complications Upper Limb Fracture	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Metabolism and nutrition disorders Dehydration	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Metabolism and nutrition disorders Hypoglycaemia	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Back Pain	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Intervertebral Disc Degeneration	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign Neoplasm Of Thyroid Gland	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.81% 2/246 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer Stage 0	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasopharyngeal Cancer	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Cancer	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Neoplasm	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Epilepsy	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Grand Mal Convulsion	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Hypoaesthesia	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Nerve Compression	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Radial Nerve Palsy	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Psychiatric disorders Suicidal Ideation	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/251 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Renal and urinary disorders Hydronephrosis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Renal and urinary disorders Nephrolithiasis	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Renal and urinary disorders Urethral Stenosis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Respiratory, thoracic and mediastinal disorders Bronchitis Chronic	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.40% 1/248 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.41% 1/246 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Hepatobiliary disorders Hepatic failure	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Gastroenteritis viral	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Cervical myelopathy	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Hepatic encephalopathy	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Psychiatric disorders Panic attack	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.9% 1/53 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Reproductive system and breast disorders Pelvic haematoma	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Other adverse events

Measure	Lira 1.8 (Weeks 0-104) n=246 participants at risk Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension period (weeks 52-104)	Lira 1.2 (Weeks 0-104) n=251 participants at risk Liraglutide 1.2 mg once daily + glimepiride placebo 8mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension period (weeks 52-104)	Glimepiride (Weeks 0-104) n=248 participants at risk Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension period (weeks 52-104)	Lira 1.8 (Weeks 104-195) n=62 participants at risk Open-label liraglutide 1.8 mg once daily in the additional extension period (weeks 104-195)	Lira 1.2 (Weeks 104-195) n=53 participants at risk Open-label liraglutide 1.2 mg once daily in the additional extension period (weeks 104-195)	Glimepiride (Weeks 104-195) n=28 participants at risk Open-label glimepiride 8 mg once daily in the additional extension period (weeks 104-195)
Infections and infestations Urinary tract infection	5.7% 14/246 • Number of events 18 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	10.4% 26/251 • Number of events 35 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.2% 13/248 • Number of events 15 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.7% 6/62 • Number of events 8 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.5% 4/53 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Nasopharyngitis	6.5% 16/246 • Number of events 21 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.2% 23/251 • Number of events 26 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.3% 18/248 • Number of events 19 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Bronchitis	3.7% 9/246 • Number of events 12 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.0% 15/251 • Number of events 17 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.4% 11/248 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.5% 4/62 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.8% 2/53 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Headache	7.3% 18/246 • Number of events 26 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	11.2% 28/251 • Number of events 53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.3% 23/248 • Number of events 30 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.8% 2/53 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	10.7% 3/28 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Nervous system disorders Dizziness	7.7% 19/246 • Number of events 21 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.2% 13/251 • Number of events 19 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.2% 13/248 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Back pain	6.9% 17/246 • Number of events 18 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.2% 18/251 • Number of events 21 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.9% 17/248 • Number of events 17 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.8% 3/62 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.5% 4/53 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 6/246 • Number of events 6 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.4% 11/251 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.0% 15/248 • Number of events 15 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Musculoskeletal and connective tissue disorders Pain in extremity	6.1% 15/246 • Number of events 15 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 9/251 • Number of events 10 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.2% 8/248 • Number of events 9 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 1/62 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.7% 3/53 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
General disorders Fatigue	5.3% 13/246 • Number of events 15 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.2% 8/251 • Number of events 9 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 9/248 • Number of events 10 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Nausea	30.5% 75/246 • Number of events 117 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	28.7% 72/251 • Number of events 97 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.5% 21/248 • Number of events 31 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Diarrhoea	19.5% 48/246 • Number of events 66 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	17.5% 44/251 • Number of events 75 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.3% 23/248 • Number of events 37 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.1% 5/62 • Number of events 9 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.7% 3/53 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Vomiting	10.2% 25/246 • Number of events 36 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	13.1% 33/251 • Number of events 38 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.0% 10/248 • Number of events 12 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Constipation	11.8% 29/246 • Number of events 35 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.4% 21/251 • Number of events 24 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.8% 12/248 • Number of events 12 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Flatulence	5.3% 13/246 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.6% 4/251 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	2.0% 5/248 • Number of events 5 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Upper respiratory tract infection	13.0% 32/246 • Number of events 42 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	14.3% 36/251 • Number of events 48 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.9% 22/248 • Number of events 30 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	12.9% 8/62 • Number of events 9 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	15.1% 8/53 • Number of events 10 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Influenza	11.0% 27/246 • Number of events 37 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.2% 23/251 • Number of events 35 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.5% 21/248 • Number of events 27 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.8% 3/62 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	9.4% 5/53 • Number of events 8 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.1% 2/28 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Sinusitis	7.3% 18/246 • Number of events 31 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	8.4% 21/251 • Number of events 25 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.3% 18/248 • Number of events 24 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.5% 4/62 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	1.9% 1/53 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Respiratory, thoracic and mediastinal disorders Cough	5.7% 14/246 • Number of events 16 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	2.0% 5/251 • Number of events 6 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.4% 11/248 • Number of events 13 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.2% 2/62 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.7% 3/53 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Psychiatric disorders Depression	5.7% 14/246 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.2% 8/251 • Number of events 11 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	2.0% 5/248 • Number of events 5 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/62 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/53 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/28 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Vascular disorders Hypertension	4.5% 11/246 • Number of events 11 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	5.6% 14/251 • Number of events 14 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.9% 17/248 • Number of events 19 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.2% 2/62 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	11.3% 6/53 • Number of events 6 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.1% 2/28 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Gastrointestinal disorders Gastritis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	4.8% 3/62 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.8% 2/53 • Number of events 2 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	7.1% 2/28 • Number of events 3 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
Infections and infestations Pharyngitis	0.00% 0/246 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/251 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	0.00% 0/248 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	6.5% 4/62 • Number of events 7 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.8% 2/53 • Number of events 4 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.	3.6% 1/28 • Number of events 1 • The adverse events were collected in a time span of 195 weeks. The full safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Additional Information

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• Principal investigator is a sponsor employee Novo Nordisk reserves the right to not release data until specified milestones. This includes the right to not release interim results, because the release of such information can invalidate the results of the entire trial. At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
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Restriction type: OTHER