Trial Outcomes & Findings for Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE™ - Diabetes (NCT NCT01272232)

Last Updated: 2017-12-29

Results Overview

Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

846 participants

Primary outcome timeframe

Week 0, week 56

Results posted on

2017-12-29

Participant Flow

A total of 126 sites in 9 countries participated: France (7), Germany (10), Israel (5), South Africa (6), Spain (8), Sweden (5), Turkey (3), United Kingdom (15), United States (67).

If eligible based on screened assessments, subjects were randomised to 1 of the 3 treatment arms in a 2:1:1 manner (liraglutide 3.0 mg, liraglutide 1.8 mg and placebo, respectively).

Participant milestones

Participant milestones
Measure	Liraglutide 3.0 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Weeks 0-56 STARTED	423	211	212
Weeks 0-56 Exposed	422	210	212
Weeks 0-56 COMPLETED	324	164	140
Weeks 0-56 NOT COMPLETED	99	47	72
Off Drug Follow-up Period (Weeks 56-68) STARTED	324	164	140
Off Drug Follow-up Period (Weeks 56-68) COMPLETED	310	154	135
Off Drug Follow-up Period (Weeks 56-68) NOT COMPLETED	14	10	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Liraglutide 3.0 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Weeks 0-56 Adverse Event	39	18	7
Weeks 0-56 Lack of Efficacy	0	0	3
Weeks 0-56 Protocol Violation	12	8	13
Weeks 0-56 Withdrawal criteria	32	14	37
Weeks 0-56 Unclassified	16	7	12
Off Drug Follow-up Period (Weeks 56-68) Adverse Event	1	1	0
Off Drug Follow-up Period (Weeks 56-68) Lack of Efficacy	1	0	0
Off Drug Follow-up Period (Weeks 56-68) Protocol Violation	1	0	1
Off Drug Follow-up Period (Weeks 56-68) Withdrawal criteria	9	7	4
Off Drug Follow-up Period (Weeks 56-68) Unclassified	2	2	0

Baseline Characteristics

Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE™ - Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Liraglutide 3.0 mg n=423 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=212 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Total n=846 Participants Total of all reporting groups
Age, Continuous	55.0 years STANDARD_DEVIATION 10.8 • n=5 Participants	54.9 years STANDARD_DEVIATION 10.7 • n=7 Participants	54.7 years STANDARD_DEVIATION 9.8 • n=5 Participants	54.9 years STANDARD_DEVIATION 10.5 • n=4 Participants
Sex: Female, Male Female	203 Participants n=5 Participants	103 Participants n=7 Participants	115 Participants n=5 Participants	421 Participants n=4 Participants
Sex: Female, Male Male	220 Participants n=5 Participants	108 Participants n=7 Participants	97 Participants n=5 Participants	425 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	46 Participants n=5 Participants	17 Participants n=7 Participants	24 Participants n=5 Participants	87 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	375 Participants n=5 Participants	194 Participants n=7 Participants	187 Participants n=5 Participants	756 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	19 Participants n=4 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
Race (NIH/OMB) Black or African American	44 Participants n=5 Participants	27 Participants n=7 Participants	27 Participants n=5 Participants	98 Participants n=4 Participants
Race (NIH/OMB) White	353 Participants n=5 Participants	177 Participants n=7 Participants	175 Participants n=5 Participants	705 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Age group 18- < 40 years	38 participants n=5 Participants	15 participants n=7 Participants	13 participants n=5 Participants	66 participants n=4 Participants
Age group 40- < 65 years	300 participants n=5 Participants	162 participants n=7 Participants	161 participants n=5 Participants	623 participants n=4 Participants
Age group 65- < 75 years	74 participants n=5 Participants	32 participants n=7 Participants	36 participants n=5 Participants	142 participants n=4 Participants
Age group >= 75 years	11 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	15 participants n=4 Participants
Fasting body weight	105.7 kg STANDARD_DEVIATION 21.9 • n=5 Participants	105.8 kg STANDARD_DEVIATION 21.0 • n=7 Participants	106.5 kg STANDARD_DEVIATION 21.3 • n=5 Participants	105.9 kg STANDARD_DEVIATION 21.5 • n=4 Participants
Height	1.69 m STANDARD_DEVIATION 0.11 • n=5 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=7 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=5 Participants	1.69 m STANDARD_DEVIATION 0.10 • n=4 Participants
Body Mass Index (BMI)	37.1 kg/m^2 STANDARD_DEVIATION 6.5 • n=5 Participants	37.0 kg/m^2 STANDARD_DEVIATION 6.9 • n=7 Participants	37.4 kg/m^2 STANDARD_DEVIATION 7.1 • n=5 Participants	37.1 kg/m^2 STANDARD_DEVIATION 6.8 • n=4 Participants
Body Mass Index (BMI) group 25.0-29.9 kg/m^2 - pre-obese	52 participants n=5 Participants	34 participants n=7 Participants	30 participants n=5 Participants	116 participants n=4 Participants
Body Mass Index (BMI) group 30.0-34.9 kg/m^2 - obese class I	139 participants n=5 Participants	62 participants n=7 Participants	59 participants n=5 Participants	260 participants n=4 Participants
Body Mass Index (BMI) group 35.0-39.9 kg/m^2 - obese class II	108 participants n=5 Participants	50 participants n=7 Participants	60 participants n=5 Participants	218 participants n=4 Participants
Body Mass Index (BMI) group >40.0 kg/m^2 - obese class III	124 participants n=5 Participants	65 participants n=7 Participants	63 participants n=5 Participants	252 participants n=4 Participants
HbA1c (glycosylated haemoglobin)	7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.0 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=7 Participants	7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=4 Participants
Fasting plasma glucose	8.8 mmol/L STANDARD_DEVIATION 1.9 • n=5 Participants	8.9 mmol/L STANDARD_DEVIATION 2.0 • n=7 Participants	8.6 mmol/L STANDARD_DEVIATION 1.8 • n=5 Participants	8.8 mmol/L STANDARD_DEVIATION 1.9 • n=4 Participants
Co-morbid hypertension Present	293 participants n=5 Participants	148 participants n=7 Participants	145 participants n=5 Participants	586 participants n=4 Participants
Co-morbid hypertension Absent	130 participants n=5 Participants	63 participants n=7 Participants	67 participants n=5 Participants	260 participants n=4 Participants
Co-morbid dyslipidaemia Present	295 participants n=5 Participants	143 participants n=7 Participants	126 participants n=5 Participants	564 participants n=4 Participants
Co-morbid dyslipidaemia Absent	128 participants n=5 Participants	68 participants n=7 Participants	86 participants n=5 Participants	282 participants n=4 Participants
Duration of diabetes	7.54 years STANDARD_DEVIATION 5.65 • n=5 Participants	7.43 years STANDARD_DEVIATION 5.16 • n=7 Participants	6.71 years STANDARD_DEVIATION 5.07 • n=5 Participants	7.30 years STANDARD_DEVIATION 5.39 • n=4 Participants

PRIMARY outcome

Timeframe: Week 0, week 56

Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change (%) From Baseline in Body Weight (Fasting)	-5.9 percent change Standard Deviation 5.5	-4.6 percent change Standard Deviation 5.5	-2.0 percent change Standard Deviation 4.3

PRIMARY outcome

Timeframe: at 56 weeks

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Proportion of Subjects Losing at Least 5% of Baseline Body Weight Yes	49.9 percentage of subjects	35.6 percentage of subjects	13.8 percentage of subjects
Proportion of Subjects Losing at Least 5% of Baseline Body Weight No	50.1 percentage of subjects	64.4 percentage of subjects	86.2 percentage of subjects

PRIMARY outcome

Timeframe: at 56 weeks

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Proportion of Subjects Losing More Than 10% of Baseline Body Weight No	76.6 percentage of subjects	85.6 percentage of subjects	95.7 percentage of subjects
Proportion of Subjects Losing More Than 10% of Baseline Body Weight Yes	23.4 percentage of subjects	14.4 percentage of subjects	4.3 percentage of subjects

SECONDARY outcome

Timeframe: Week 0, week 56

Change in HbA1c (%-points) was calculated as the difference between the HbA1c (%) at Week 0 and Week 56.

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c)	-1.3 percentage point change of HbA1c Standard Deviation 0.9	-1.1 percentage point change of HbA1c Standard Deviation 1.0	-0.3 percentage point change of HbA1c Standard Deviation 0.9

SECONDARY outcome

Timeframe: at 56 weeks

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Proportion of Subjects Reaching Target HbA1c Below 7% Yes	69.2 percentage of subjects	66.7 percentage of subjects	27.2 percentage of subjects
Proportion of Subjects Reaching Target HbA1c Below 7% No	30.8 percentage of subjects	33.3 percentage of subjects	72.8 percentage of subjects

SECONDARY outcome

Timeframe: at 56 weeks

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% Yes	56.5 percentage of subjects	45.6 percentage of subjects	15.0 percentage of subjects
Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% No	43.5 percentage of subjects	54.4 percentage of subjects	85.0 percentage of subjects

SECONDARY outcome

Timeframe: Week 0, week 56

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=412 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=204 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=211 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change From Baseline in Waist Circumference	-6.1 cm Standard Deviation 6.5	-4.8 cm Standard Deviation 5.6	-2.7 cm Standard Deviation 5.4

SECONDARY outcome

Timeframe: Week 0, week 68

Population: Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=324 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=164 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=140 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change (%) From Baseline in Body Weight (Fasting)	-4.7 percent change Standard Deviation 5.0	-3.6 percent change Standard Deviation 5.7	-2.7 percent change Standard Deviation 5.8

SECONDARY outcome

Timeframe: Week 56, week 68

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=324 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=164 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=140 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change (%) From Week 56 to 68 in Body Weight (Fasting)	2.3 percent change Standard Deviation 2.9	2.0 percent change Standard Deviation 2.9	-0.1 percent change Standard Deviation 2.2

SECONDARY outcome

Timeframe: Week 0, week 68

Population: Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=324 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=164 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=140 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change From Baseline in Waist Circumference	-5.7 cm Standard Deviation 6.3	-4.4 cm Standard Deviation 6.0	-3.2 cm Standard Deviation 6.8

SECONDARY outcome

Timeframe: Week 56, week 68

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=324 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=164 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=140 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Change From Week 56 to 68 in Waist Circumference	1.21 cm Standard Deviation 3.94	1.02 cm Standard Deviation 3.55	-0.22 cm Standard Deviation 3.23

SECONDARY outcome

Timeframe: Weeks 0-56

Population: Safety analysis set, comprising all randomised subjects who had been exposed to at least one dose of trial product.

Hypoglycaemic episodes were classified according to American Diabetes Association (ADA) definitions as well as to the Novo Nordisk definition of a minor hypoglycaemic event (blood glucose level below approximately 2.8 mmol/L \[50 mg/dL\] or plasma glucose level below 3.1 mmol/L \[56 mg/dL\]).

Outcome measures

Outcome measures
Measure	Liraglutide 3.0 mg n=422 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=210 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=212 Participants Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Incidence of Hypoglycaemic Episodes ADA: Relative	17 Episodes/100 years of patient exposure	16 Episodes/100 years of patient exposure	5 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes ADA: Unclassifiable	14 Episodes/100 years of patient exposure	7 Episodes/100 years of patient exposure	3 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes Minor	34 Episodes/100 years of patient exposure	46 Episodes/100 years of patient exposure	13 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes ADA: Severe	1 Episodes/100 years of patient exposure	2 Episodes/100 years of patient exposure	0 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes ADA: Documented, symptomatic	87 Episodes/100 years of patient exposure	95 Episodes/100 years of patient exposure	31 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes ADA: Asymptomatic	151 Episodes/100 years of patient exposure	142 Episodes/100 years of patient exposure	46 Episodes/100 years of patient exposure
Incidence of Hypoglycaemic Episodes ADA: Probable, symptomatic	2 Episodes/100 years of patient exposure	2 Episodes/100 years of patient exposure	1 Episodes/100 years of patient exposure

Adverse Events

Liraglutide 3.0 mg

Serious events: 37 serious events

Other events: 361 other events

Deaths: 0 deaths

Liraglutide 1.8 mg

Serious events: 18 serious events

Other events: 173 other events

Deaths: 0 deaths

Liraglutide Placebo

Serious events: 13 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Novo Nordisk reserves the right not to release data until specified milestones are available. This includes the right not to release interim results from clinical trials, as such results may lead to conclusions that are later proven incorrect. At the end of the trial, one or more manuscripts for publication will be prepared in collaboration between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to briefly postpone publication or communication to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Measure	Liraglutide 3.0 mg n=422 participants at risk Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide 1.8 mg n=210 participants at risk Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.	Liraglutide Placebo n=212 participants at risk Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%.
Gastrointestinal disorders Abdominal distension	6.2% 26/422 • Number of events 32 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	4.8% 10/210 • Number of events 11 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	1.4% 3/212 • Number of events 3 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Abdominal pain	6.2% 26/422 • Number of events 34 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	1.9% 4/210 • Number of events 4 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	4.2% 9/212 • Number of events 9 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Abdominal pain upper	3.6% 15/422 • Number of events 21 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	6.7% 14/210 • Number of events 17 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	0.94% 2/212 • Number of events 2 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Constipation	16.1% 68/422 • Number of events 78 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	9.5% 20/210 • Number of events 24 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	6.1% 13/212 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Diarrhoea	25.6% 108/422 • Number of events 173 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	17.6% 37/210 • Number of events 50 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	12.7% 27/212 • Number of events 35 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Dyspepsia	11.1% 47/422 • Number of events 59 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	6.7% 14/210 • Number of events 16 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	2.4% 5/212 • Number of events 5 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Flatulence	5.2% 22/422 • Number of events 26 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	3.8% 8/210 • Number of events 8 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	1.9% 4/212 • Number of events 4 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Nausea	32.7% 138/422 • Number of events 208 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	31.4% 66/210 • Number of events 84 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	13.7% 29/212 • Number of events 34 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Gastrointestinal disorders Vomiting	15.6% 66/422 • Number of events 113 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	10.0% 21/210 • Number of events 27 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/212 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
General disorders Fatigue	8.3% 35/422 • Number of events 45 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.2% 11/210 • Number of events 11 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	3.3% 7/212 • Number of events 7 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
General disorders Injection site haematoma	4.5% 19/422 • Number of events 33 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	1.9% 4/210 • Number of events 4 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/212 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Bronchitis	3.1% 13/422 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/210 • Number of events 16 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.2% 11/212 • Number of events 15 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Influenza	5.2% 22/422 • Number of events 24 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/210 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	7.1% 15/212 • Number of events 16 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Nasopharyngitis	20.9% 88/422 • Number of events 134 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	16.2% 34/210 • Number of events 46 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	19.3% 41/212 • Number of events 54 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Sinusitis	3.8% 16/422 • Number of events 19 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	7.1% 15/210 • Number of events 18 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	8.5% 18/212 • Number of events 22 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Upper respiratory tract infection	9.5% 40/422 • Number of events 49 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	11.0% 23/210 • Number of events 25 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	8.5% 18/212 • Number of events 19 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Infections and infestations Urinary tract infection	4.5% 19/422 • Number of events 34 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	6.2% 13/210 • Number of events 17 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/212 • Number of events 14 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Investigations Lipase increased	11.8% 50/422 • Number of events 56 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	10.5% 22/210 • Number of events 26 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	6.6% 14/212 • Number of events 16 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Metabolism and nutrition disorders Decreased appetite	9.5% 40/422 • Number of events 44 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	11.0% 23/210 • Number of events 23 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	1.9% 4/212 • Number of events 4 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Metabolism and nutrition disorders Hypoglycaemia	44.3% 187/422 • Number of events 981 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	40.0% 84/210 • Number of events 429 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	27.8% 59/212 • Number of events 154 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 30/422 • Number of events 42 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	8.1% 17/210 • Number of events 25 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/212 • Number of events 15 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Back pain	10.0% 42/422 • Number of events 67 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	12.9% 27/210 • Number of events 36 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	9.4% 20/212 • Number of events 27 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.2% 22/422 • Number of events 24 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	4.3% 9/210 • Number of events 10 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	2.8% 6/212 • Number of events 7 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 16/422 • Number of events 20 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/210 • Number of events 13 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	4.7% 10/212 • Number of events 12 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Nervous system disorders Dizziness	7.1% 30/422 • Number of events 39 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	4.8% 10/210 • Number of events 15 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	2.8% 6/212 • Number of events 7 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Nervous system disorders Headache	15.6% 66/422 • Number of events 125 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	12.4% 26/210 • Number of events 42 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	13.7% 29/212 • Number of events 40 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Respiratory, thoracic and mediastinal disorders Cough	4.3% 18/422 • Number of events 21 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.7% 12/210 • Number of events 16 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	3.8% 8/212 • Number of events 9 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.
Vascular disorders Hypertension	2.8% 12/422 • Number of events 12 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	3.3% 7/210 • Number of events 8 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.	5.2% 11/212 • Number of events 12 • Adverse events were recorded for up to 68 weeks. Safety Analysis Set comprising all randomised subjects who had been exposed to at least one dose of trial product.