Trial Outcomes & Findings for To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together (NCT NCT00318461)

NCT ID: NCT00318461

Last Updated: 2017-03-07

Results Overview

Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1091 participants
• Primary outcome timeframe: week 0, week 26
• Results posted on: 2017-03-07

Participant Flow

A total of 170 centres in 21 countries: Argentina (4), Australia (19), Belgium (6), Bulgaria (1), Germany (33), Denmark (9), Spain (14), United Kingdom (11), Croatia (2), Hungary (5), Ireland (4), India (5), Italy (10), The Netherlands (5), New Zealand (3), Norway (8), Romania (3), Russia (6), Sweden (8), Slovakia (7) and South Africa (7)

Eligible subjects discontinued their oral anti-diabetic drug treatment and commenced a 3-week period of forced titration of metformin followed by a 3-week maintenance period. Subjects on current metformin therapy could go through a modified titration period or advance directly to the 3-week maintenance period at the discretion of the investigator.

Participant milestones

Measure	Lira 0.6 + Met Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Double-Blind, 6 Months STARTED	242	241	242	122	244
Double-Blind, 6 Months Exposed to Study Drug	242	240	242	121	242
Double-Blind, 6 Months COMPLETED	208	197	191	74	210
Double-Blind, 6 Months NOT COMPLETED	34	44	51	48	34
Open-Label Extension, 18 Months STARTED	208	197	191	74	210
Open-Label Extension, 18 Months COMPLETED	130	137	118	31	113
Open-Label Extension, 18 Months NOT COMPLETED	78	60	73	43	97

Reasons for withdrawal

Measure	Lira 0.6 + Met Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Double-Blind, 6 Months Adverse Event	11	23	29	2	8
Double-Blind, 6 Months Lack of Efficacy	19	8	13	29	9
Double-Blind, 6 Months Protocol Violation	2	4	4	4	5
Double-Blind, 6 Months Lost to follow up	0	1	0	0	0
Double-Blind, 6 Months Poor compliance/Non-compliance	0	1	0	0	0
Double-Blind, 6 Months Consent withdrawn	0	3	4	10	4
Double-Blind, 6 Months Subject decision/No wish to continue	0	2	1	0	2
Double-Blind, 6 Months Move	0	1	0	0	0
Double-Blind, 6 Months Tendency to low blood glucose levels	0	0	0	0	1
Double-Blind, 6 Months FPG exceeds limits/too high	1	0	0	2	0
Double-Blind, 6 Months Work commitment	0	0	0	0	1
Double-Blind, 6 Months Investigator decision	0	0	0	0	1
Double-Blind, 6 Months Lack of time	1	0	0	0	0
Double-Blind, 6 Months Hypoglycaemia/Hypoglycemia	0	0	0	0	2
Double-Blind, 6 Months Hyperglicaemia	0	0	0	1	0
Double-Blind, 6 Months metformin titrated <1500 mg or >2000 mg	0	0	0	0	1
Double-Blind, 6 Months Fear of experiencing AE again	0	1	0	0	0
Open-Label Extension, 18 Months Withdrawals between 6 and 24 months	19	14	27	11	22
Open-Label Extension, 18 Months Adverse Event	11	8	6	1	6
Open-Label Extension, 18 Months Lack of Efficacy	41	33	37	27	63
Open-Label Extension, 18 Months Protocol Violation	7	5	3	4	6

Baseline Characteristics

To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together

Baseline characteristics by cohort

Measure	Lira 0.6 + Met n=242 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=240 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=242 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=242 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Total n=1087 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 10.5 • n=5 Participants	57.2 years STANDARD_DEVIATION 9.2 • n=7 Participants	56.8 years STANDARD_DEVIATION 9.4 • n=5 Participants	56.0 years STANDARD_DEVIATION 9.4 • n=4 Participants	57.3 years STANDARD_DEVIATION 8.8 • n=21 Participants	56.7 years STANDARD_DEVIATION 9.5 • n=10 Participants
Sex: Female, Male Female	91 Participants n=5 Participants	111 Participants n=7 Participants	100 Participants n=5 Participants	49 Participants n=4 Participants	103 Participants n=21 Participants	454 Participants n=10 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	129 Participants n=7 Participants	142 Participants n=5 Participants	72 Participants n=4 Participants	139 Participants n=21 Participants	633 Participants n=10 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	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	31 Participants n=5 Participants	19 Participants n=7 Participants	18 Participants n=5 Participants	9 Participants n=4 Participants	21 Participants n=21 Participants	98 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	26 Participants n=10 Participants
Race (NIH/OMB) White	202 Participants n=5 Participants	210 Participants n=7 Participants	214 Participants n=5 Participants	106 Participants n=4 Participants	214 Participants n=21 Participants	946 Participants n=10 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	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	17 Participants n=10 Participants
Previous anti-diabetic treatment Mono-therapy	81 participants n=5 Participants	90 participants n=7 Participants	82 participants n=5 Participants	41 participants n=4 Participants	90 participants n=21 Participants	384 participants n=10 Participants
Previous anti-diabetic treatment Combination therapy	161 participants n=5 Participants	150 participants n=7 Participants	160 participants n=5 Participants	80 participants n=4 Participants	152 participants n=21 Participants	703 participants n=10 Participants
BMI	30.5 kg/m2 STANDARD_DEVIATION 4.8 • n=5 Participants	31.1 kg/m2 STANDARD_DEVIATION 4.8 • n=7 Participants	30.9 kg/m2 STANDARD_DEVIATION 4.6 • n=5 Participants	31.6 kg/m2 STANDARD_DEVIATION 4.4 • n=4 Participants	31.2 kg/m2 STANDARD_DEVIATION 4.6 • n=21 Participants	31.0 kg/m2 STANDARD_DEVIATION 4.7 • n=10 Participants
Duration of diabetes	7.0 years STANDARD_DEVIATION 4.8 • n=5 Participants	6.8 years STANDARD_DEVIATION 4.9 • n=7 Participants	7.8 years STANDARD_DEVIATION 5.2 • n=5 Participants	7.9 years STANDARD_DEVIATION 6.0 • n=4 Participants	7.7 years STANDARD_DEVIATION 5.3 • n=21 Participants	7.4 years STANDARD_DEVIATION 5.2 • n=10 Participants
HbA1c	8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.3 percentage of total haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.3 percentage of total haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.4 percentage of total haemoglobin STANDARD_DEVIATION 1.0 • n=4 Participants	8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 • n=21 Participants	8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 • n=10 Participants
Height	1.69 m STANDARD_DEVIATION 0.10 • n=5 Participants	1.68 m STANDARD_DEVIATION 0.11 • n=7 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=5 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=4 Participants	1.69 m STANDARD_DEVIATION 0.11 • n=21 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=10 Participants

PRIMARY outcome

Timeframe: week 0, week 26

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 A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)

Outcome measures

Measure	Lira 0.6 + Met n=239 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=232 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=236 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=120 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=234 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Glycosylated A1c (HbA1c) at Week 26	-0.69 Percentage point of total HbA1c Standard Error 0.07	-0.97 Percentage point of total HbA1c Standard Error 0.07	-1.00 Percentage point of total HbA1c Standard Error 0.07	0.09 Percentage point of total HbA1c Standard Error 0.09	-0.98 Percentage point of total HbA1c Standard Error 0.07

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.

Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)

Outcome measures

Measure	Lira 0.6 + Met n=239 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=231 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=235 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=120 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=234 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Glycosylated A1c (HbA1c) at Week 104	-0.36 percentage of total haemoglobin Standard Error 0.08	-0.56 percentage of total haemoglobin Standard Error 0.08	-0.58 percentage of total haemoglobin Standard Error 0.08	0.25 percentage of total haemoglobin Standard Error 0.10	-0.50 percentage of total haemoglobin Standard Error 0.08

SECONDARY outcome

Timeframe: week 0, week 26

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 26 weeks (end of randomisation)

Outcome measures

Measure	Lira 0.6 + Met n=242 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=236 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=241 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=237 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Body Weight at Week 26	-1.78 kg Standard Error 0.23	-2.58 kg Standard Error 0.24	-2.79 kg Standard Error 0.23	-1.51 kg Standard Error 0.31	0.95 kg Standard Error 0.23

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 treatment)

Outcome measures

Measure	Lira 0.6 + Met n=242 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=236 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=241 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=237 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Body Weight at Week 104	-2.07 kg Standard Error 0.28	-3.03 kg Standard Error 0.29	-2.91 kg Standard Error 0.28	-1.80 kg Standard Error 0.38	0.70 kg Standard Error 0.29

SECONDARY outcome

Timeframe: week 0, week 26

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 26 weeks (end of randomisation)

Outcome measures

Measure	Lira 0.6 + Met n=238 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=234 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=235 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=116 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=234 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Fasting Plasma Glucose (FPG) at Week 26	-1.13 mmol/L Standard Error 0.15	-1.63 mmol/L Standard Error 0.16	-1.68 mmol/L Standard Error 0.15	0.40 mmol/L Standard Error 0.21	-1.31 mmol/L Standard Error 0.16

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 treatment)

Outcome measures

Measure	Lira 0.6 + Met n=238 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=233 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=234 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=116 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=234 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Fasting Plasma Glucose (FPG) at Week 104	-0.80 mmol/L Standard Error 0.17	-1.20 mmol/L Standard Error 0.18	-1.18 mmol/L Standard Error 0.17	0.75 mmol/L Standard Error 0.23	-0.64 mmol/L Standard Error 0.17

SECONDARY outcome

Timeframe: week 0, week 26

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 based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.

Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.

Outcome measures

Measure	Lira 0.6 + Met n=214 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=207 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=205 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=90 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=213 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26	-0.23 mmol/l Standard Error 0.12	-0.40 mmol/l Standard Error 0.13	-0.56 mmol/l Standard Error 0.12	-0.44 mmol/l Standard Error 0.18	-0.44 mmol/l Standard Error 0.12

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 based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.

Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.

Outcome measures

Measure	Lira 0.6 + Met n=218 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=208 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=206 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=90 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=215 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104	-0.27 mmol/L Standard Error 0.12	-0.56 mmol/L Standard Error 0.13	-0.44 mmol/L Standard Error 0.13	-0.20 mmol/L Standard Error 0.18	-0.29 mmol/L Standard Error 0.13

SECONDARY outcome

Timeframe: week 0, week 26

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 post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.

Outcome measures

Measure	Lira 0.6 + Met n=214 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=207 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=205 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=90 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=214 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26	-1.68 mmol/L Standard Error 0.16	-2.33 mmol/L Standard Error 0.17	-2.57 mmol/L Standard Error 0.16	-0.62 mmol/L Standard Error 0.24	-2.46 mmol/L Standard Error 0.16

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 post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.

Outcome measures

Measure	Lira 0.6 + Met n=218 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=208 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=206 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=90 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=216 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104	-1.59 mmol/L Standard Error 0.18	-2.22 mmol/L Standard Error 0.18	-2.10 mmol/L Standard Error 0.18	-0.43 mmol/L Standard Error 0.26	-1.80 mmol/L Standard Error 0.18

SECONDARY outcome

Timeframe: week 0, week 26

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 beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).

Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).

Outcome measures

Measure	Lira 0.6 + Met n=229 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=224 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=224 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=109 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=226 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Beta-cell Function at Week 26	20.45 percentage point (%point) Standard Error 5.19	20.33 percentage point (%point) Standard Error 5.34	26.12 percentage point (%point) Standard Error 5.20	-1.63 percentage point (%point) Standard Error 7.19	24.68 percentage point (%point) Standard Error 5.25

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 beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).

Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).

Outcome measures

Measure	Lira 0.6 + Met n=230 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=224 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=224 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=110 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=226 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Change in Beta-cell Function at Week 104	64.48 percentage point (%point) Standard Error 24.93	27.30 percentage point (%point) Standard Error 25.70	17.81 percentage point (%point) Standard Error 25.03	-7.89 percentage point (%point) Standard Error 34.47	11.25 percentage point (%point) Standard Error 25.27

SECONDARY outcome

Timeframe: weeks 0-26

Population: Safety analysis set is all randomised subjects who were exposed to at least one dose of study product.

Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Outcome measures

Measure	Lira 0.6 + Met n=242 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=240 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=242 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=242 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Hypoglycaemic Episodes at Week 26 Major	0 episodes	0 episodes	0 episodes	0 episodes	0 episodes
Hypoglycaemic Episodes at Week 26 Minor	15 episodes	3 episodes	9 episodes	6 episodes	136 episodes
Hypoglycaemic Episodes at Week 26 Symptoms only	17 episodes	7 episodes	22 episodes	10 episodes	175 episodes

SECONDARY outcome

Timeframe: weeks 0-104

Population: Safety analysis set is all randomised subjects who were exposed to at least one dose of study product.

Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end of treatment). 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Outcome measures

Measure	Lira 0.6 + Met n=242 Participants Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=240 Participants Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=242 Participants Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 Participants Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=242 Participants Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Hypoglycaemic Episodes at Week 104 All	52 episodes	51 episodes	49 episodes	18 episodes	524 episodes
Hypoglycaemic Episodes at Week 104 Major	0 episodes	1 episodes	0 episodes	0 episodes	0 episodes
Hypoglycaemic Episodes at Week 104 Minor	23 episodes	26 episodes	22 episodes	6 episodes	284 episodes
Hypoglycaemic Episodes at Week 104 Symptoms only	29 episodes	24 episodes	27 episodes	12 episodes	240 episodes

Adverse Events

Lira 0.6 + Met

Serious events: 36 serious events

Other events: 132 other events

Deaths: 0 deaths

Lira 1.2 + Met

Serious events: 25 serious events

Other events: 144 other events

Deaths: 0 deaths

Lira 1.8 + Met

Serious events: 16 serious events

Other events: 158 other events

Deaths: 0 deaths

Met Mono

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Met + Glim

Serious events: 24 serious events

Other events: 128 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lira 0.6 + Met n=242 participants at risk Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=240 participants at risk Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=242 participants at risk Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 participants at risk Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=242 participants at risk Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Cardiac disorders Angina pectoris	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/240 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Acute myocardial infarction	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Myocardial infarction	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Atrial fibrillation	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Coronary artery disease	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Acute coronary syndrome	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Atrial flutter	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Cardiac arrest	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Cardiac failure	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Coronary artery occlusion	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Myocardial ischaemia	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Right ventricular failure	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Tachycardia paroxysmal	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Cardiac disorders Ventricular tachycardia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Fall	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	1.7% 2/121 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Concussion	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Road traffic accident	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Femur fracture	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Hip fracture	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Joint injury	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Sympathetic nerve injury	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Injury, poisoning and procedural complications Wound	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Inguinal hernia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Femoral hernia, obstructive	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Gastric ulcer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Gastritis	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Hiatus hernia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Mallory-Weiss syndrome	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Pancreatitis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Umbilical hernia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/240 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Muscle disorder	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Osteolysis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Tendon disorder	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Pyelonephritis	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Abscess sweat gland	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Erysipelas	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Infected skin ulcer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Infection	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Osteomyelitis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Tuberculosis	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Upper respiratory tract infection	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Wound sepsis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified recurrent	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant lymphoma unclassifiable high grade	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Carotid artery stenosis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Cerebral hypoperfusion	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Cerebrovascular accident	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Diabetic neuropathy	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Haemorrhage intracranial	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Headache	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Endocrine disorders Goitre	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Endocrine disorders Autoimmune thyroiditis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Renal and urinary disorders Nephrolithiasis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Renal and urinary disorders Renal failure acute	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Renal and urinary disorders Calculus ureteric	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Snoring	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
General disorders Hernia	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
General disorders Chest pain	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
General disorders Pyrexia	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Eye disorders Cataract	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Eye disorders Uveitis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Investigations Blood calcitonin increased	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Investigations Electrocardiogram abnormal	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Investigations Heart rate increased	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Reproductive system and breast disorders Menorrhagia	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Reproductive system and breast disorders Testicular pain	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Skin and subcutaneous tissue disorders Penile ulceration	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Vascular disorders Arterial stenosis limb	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Vascular disorders Arteriosclerosis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Vascular disorders Circulatory collapse	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Ear and labyrinth disorders Vertigo	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Metabolism and nutrition disorders Hypoglycaemia	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/240 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.42% 1/240 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.

Other adverse events

Measure	Lira 0.6 + Met n=242 participants at risk Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.2 + Met n=240 participants at risk Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Lira 1.8 + Met n=242 participants at risk Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met Mono n=121 participants at risk Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	Met + Glim n=242 participants at risk Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)
Infections and infestations Nasopharyngitis	17.8% 43/242 • Number of events 69 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	15.0% 36/240 • Number of events 70 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	14.9% 36/242 • Number of events 43 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	9.9% 12/121 • Number of events 21 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	20.2% 49/242 • Number of events 80 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Influenza	5.8% 14/242 • Number of events 17 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.2% 15/240 • Number of events 18 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	7.0% 17/242 • Number of events 27 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 5/121 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	7.4% 18/242 • Number of events 27 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Upper respiratory tract infection	4.5% 11/242 • Number of events 16 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.8% 14/240 • Number of events 19 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.2% 15/242 • Number of events 19 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	3.3% 4/121 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.0% 12/242 • Number of events 19 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Infections and infestations Bronchitis	4.1% 10/242 • Number of events 10 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.4% 13/240 • Number of events 16 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.0% 12/242 • Number of events 13 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.5% 3/121 • Number of events 3 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.2% 15/242 • Number of events 20 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Nausea	12.4% 30/242 • Number of events 33 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	17.5% 42/240 • Number of events 50 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	21.5% 52/242 • Number of events 70 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 5/121 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 10/242 • Number of events 14 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Diarrhoea	12.8% 31/242 • Number of events 40 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	11.2% 27/240 • Number of events 43 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	16.5% 40/242 • Number of events 50 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 5/121 • Number of events 5 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.8% 14/242 • Number of events 20 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Vomiting	7.9% 19/242 • Number of events 21 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	7.5% 18/240 • Number of events 22 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	9.9% 24/242 • Number of events 26 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Dyspepsia	5.0% 12/242 • Number of events 13 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.5% 6/240 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	9.1% 22/242 • Number of events 27 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 4 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.9% 7/242 • Number of events 11 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Gastritis	4.1% 10/242 • Number of events 11 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	3.3% 8/240 • Number of events 11 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.4% 13/242 • Number of events 13 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	1.7% 4/242 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Gastrointestinal disorders Toothache	2.5% 6/242 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.4% 13/240 • Number of events 14 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.9% 7/242 • Number of events 8 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.0% 6/121 • Number of events 8 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	1.2% 3/242 • Number of events 3 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Back pain	6.6% 16/242 • Number of events 21 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.2% 15/240 • Number of events 17 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	7.0% 17/242 • Number of events 20 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 5/121 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	8.7% 21/242 • Number of events 23 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Musculoskeletal and connective tissue disorders Arthralgia	5.8% 14/242 • Number of events 15 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.1% 5/240 • Number of events 5 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	3.7% 9/242 • Number of events 12 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 5/121 • Number of events 7 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	7.9% 19/242 • Number of events 22 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Nervous system disorders Headache	10.7% 26/242 • Number of events 41 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	14.2% 34/240 • Number of events 40 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	14.5% 35/242 • Number of events 51 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.6% 8/121 • Number of events 8 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	13.2% 32/242 • Number of events 55 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Metabolism and nutrition disorders Anorexia	2.5% 6/242 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.2% 10/240 • Number of events 10 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	6.2% 15/242 • Number of events 17 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 1/121 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.41% 1/242 • Number of events 1 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Metabolism and nutrition disorders Decreased appetite	1.7% 4/242 • Number of events 4 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.8% 14/240 • Number of events 15 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.1% 10/242 • Number of events 10 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/121 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.00% 0/242 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Vascular disorders Hypertension	4.5% 11/242 • Number of events 11 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.4% 13/240 • Number of events 15 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	4.5% 11/242 • Number of events 11 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	1.7% 2/121 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.0% 12/242 • Number of events 12 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 8/242 • Number of events 9 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	2.5% 6/240 • Number of events 6 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	0.83% 2/242 • Number of events 3 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	1.7% 2/121 • Number of events 2 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.	5.4% 13/242 • Number of events 16 • Adverse events were collected over 24 months of treatment The safety analysis set is all randomised subjects who were exposed to at least one dose of study product.

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