Trial Outcomes & Findings for Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Subjects With Type 2 Diabetes (NCT NCT01336023)

NCT ID: NCT01336023

Last Updated: 2018-02-19

Results Overview

Values of mean change in HbA1c.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1663 participants

Primary outcome timeframe

Week 0, week 26

Results posted on

2018-02-19

Participant Flow

Countries: 19; Sites: 271; Number of sites as in parenthesis. Australia (7), Canada (14 ), Finland (5 ), Germany (12 ), Hungary (6), India (23), Ireland (2), Italy (6), Malaysia (5), Mexico (2 ), Russian Federation (11), Singapore (3), Slovakia (5), South Africa (13), Spain (8), Taiwan (3), Thailand (4), United Kingdom (16) and United States (126).

Subjects on metformin and/or pioglitazone treatment underwent a 26-week main trial and continued to enter an additional 26-week extension trial. Total duration of the trial was up to 55 weeks (2 weeks screening + 26 week main period + 26 week extension period + 1 week follow-up after last dose).

Participant milestones

Participant milestones
Measure	IDeg Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Week 0 to Week 26 STARTED	414	834	415
Week 0 to Week 26 Exposed	413	826	413
Week 0 to Week 26 COMPLETED	366	736	342
Week 0 to Week 26 NOT COMPLETED	48	98	73
Week 27 to 52 STARTED	333	665	313
Week 27 to 52 COMPLETED	305	621	285
Week 27 to 52 NOT COMPLETED	28	44	28

Reasons for withdrawal

Reasons for withdrawal
Measure	IDeg Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Week 0 to Week 26 Adverse Event	8	10	24
Week 0 to Week 26 Lack of Efficacy	0	1	0
Week 0 to Week 26 Protocol Violation	1	2	0
Week 0 to Week 26 Withdrawal Criteria	34	69	40
Week 0 to Week 26 Unclassified	5	16	9
Week 27 to 52 Adverse Event	1	5	2
Week 27 to 52 Protocol Violation	0	2	1
Week 27 to 52 Withdrawal Criteria	14	19	16
Week 27 to 52 Unclassified	13	18	9

Baseline Characteristics

The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDeg n=413 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=833 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=414 Participants Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Total n=1660 Participants Total of all reporting groups
Age, Continuous	54.9 years STANDARD_DEVIATION 9.7 • n=413 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.	55.1 years STANDARD_DEVIATION 9.9 • n=833 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.	55.0 years STANDARD_DEVIATION 10.2 • n=413 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.	55.0 years STANDARD_DEVIATION 9.9 • n=1659 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.
Sex: Female, Male Female	213 Participants n=413 Participants	398 Participants n=833 Participants	206 Participants n=414 Participants	817 Participants n=1660 Participants
Sex: Female, Male Male	200 Participants n=413 Participants	435 Participants n=833 Participants	208 Participants n=414 Participants	843 Participants n=1660 Participants
Body Weight	87.4 kg STANDARD_DEVIATION 19.2 • n=413 Participants	87.2 kg STANDARD_DEVIATION 19.0 • n=833 Participants	87.4 kg STANDARD_DEVIATION 18.0 • n=414 Participants	87.3 kg STANDARD_DEVIATION 18.8 • n=1660 Participants
Normalised Incremental Area under curve (AUC)	4.12 mmol/L STANDARD_DEVIATION 1.80 • n=63 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 63, 128 and 61, respectively.	4.11 mmol/L STANDARD_DEVIATION 2.05 • n=128 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 63, 128 and 61, respectively.	4.12 mmol/L STANDARD_DEVIATION 1.82 • n=61 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 63, 128 and 61, respectively.	4.11 mmol/L STANDARD_DEVIATION 1.93 • n=252 Participants • The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 63, 128 and 61, respectively.
Glycosylated haemoglobin (HbA1c)	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.0 • n=413 Participants	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=833 Participants	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=414 Participants	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=1660 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects and missing data was imputed using LOCF. Three subjects did not have their case book signed off due to discontinuation of an investigator's participation in the trial; hence 1 subject from each arm was excluded from the FAS.

Values of mean change in HbA1c.

Outcome measures

Outcome measures
Measure	IDeg n=413 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=833 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=414 Participants Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26.	-1.44 Percentage of glycosylated haemoglobin Standard Deviation 1.03	-1.91 Percentage of glycosylated haemoglobin Standard Deviation 1.07	-1.28 Percentage of glycosylated haemoglobin Standard Deviation 1.13

SECONDARY outcome

Timeframe: Week 0, Week 26

Values of mean change in body weight.

Outcome measures

Outcome measures
Measure	IDeg n=413 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=833 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=414 Participants Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Mean Change From Baseline in Body Weight at Week 26	1.6 kg Standard Deviation 4.0	-0.5 kg Standard Deviation 3.5	-3.0 kg Standard Deviation 3.5

SECONDARY outcome

Timeframe: Weeks 0-26

Population: The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators. The missing data was imputed using LOCF. The number of subjects analysed in SAS for each arm are 412, 825 and 412, respectively.

Reported hypoglycemaic episodes are number of hypoglycemic events per 100 patient years of exposure.

Outcome measures

Outcome measures
Measure	IDeg n=412 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=825 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=412 Participants Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Number of Hypoglycaemic Episodes	256.7 Events per 100 patient years of exposure	180.2 Events per 100 patient years of exposure	22.0 Events per 100 patient years of exposure

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: The number of subjects analysed were equal to study population in which the meal test was perfomed at selected sites. Missing data was imputed using LOCF.

Values of mean change in normalised iAUC0-4h values based on LOCF data derived from the glucose concentration profiles during a meal test. The meal test was performed at selected sites at baseline and after 26 weeks of treatment in the main trial period. The incremental AUC was calculated using the trapezoidal method and the resulting area was divided length of the observation period to yield the (normalised) prandial increment in mmol/L using the available valid glucose observations and the associated actual elapsed time point.

Outcome measures

Outcome measures
Measure	IDeg n=63 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=128 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=61 Participants Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Change From Baseline in Incremental Area Under the Curve 0-4h (iAUC0-4h) Derived From the Glucose Concentration Profile During Meal Test	-0.17 mmol/L Standard Deviation 1.98	-0.87 mmol/L Standard Deviation 1.65	-0.78 mmol/L Standard Deviation 1.62

SECONDARY outcome

Timeframe: Week 26

Population: The FAS included all randomised subjects. Missing data was imputed using LOCF. For 22 subjects, the dose values were missing hence did not contribute to the analysis. The comparison was made between the insulin products IDeg and IDeglira.

Mean of the actual doses recorded at visit 28 (Week 26).

Outcome measures

Outcome measures
Measure	IDeg n=408 Participants Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=816 Participants Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Mean Actual Daily Insulin Dose	53 units Standard Deviation 28	38 units Standard Deviation 13	—

Adverse Events

IDeg

Serious events: 22 serious events

Other events: 160 other events

Deaths: 0 deaths

IDegLira

Serious events: 38 serious events

Other events: 386 other events

Deaths: 0 deaths

Liraglutide

Serious events: 24 serious events

Other events: 241 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDeg n=412 participants at risk Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	IDegLira n=825 participants at risk Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	Liraglutide n=412 participants at risk Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
Gastrointestinal disorders Constipation	0.97% 4/412 • Number of events 4 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	3.2% 26/825 • Number of events 34 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.1% 21/412 • Number of events 23 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Gastrointestinal disorders Diarrhoea	6.8% 28/412 • Number of events 33 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	10.2% 84/825 • Number of events 128 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	16.3% 67/412 • Number of events 94 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Gastrointestinal disorders Dyspepsia	1.2% 5/412 • Number of events 5 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	3.4% 28/825 • Number of events 35 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.3% 22/412 • Number of events 28 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Gastrointestinal disorders Nausea	3.9% 16/412 • Number of events 21 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	10.3% 85/825 • Number of events 102 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	22.3% 92/412 • Number of events 118 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Gastrointestinal disorders Vomiting	2.4% 10/412 • Number of events 10 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.0% 41/825 • Number of events 62 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	9.0% 37/412 • Number of events 54 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Infections and infestations Nasopharyngitis	12.6% 52/412 • Number of events 74 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	13.9% 115/825 • Number of events 162 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	13.3% 55/412 • Number of events 81 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Infections and infestations Upper respiratory tract infection	8.3% 34/412 • Number of events 40 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	7.8% 64/825 • Number of events 79 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	8.0% 33/412 • Number of events 37 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Investigations Lipase increased	4.4% 18/412 • Number of events 20 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.8% 48/825 • Number of events 55 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	8.5% 35/412 • Number of events 40 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Metabolism and nutrition disorders Decreased appetite	0.49% 2/412 • Number of events 2 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	2.7% 22/825 • Number of events 23 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	7.3% 30/412 • Number of events 32 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Musculoskeletal and connective tissue disorders Arthralgia	3.6% 15/412 • Number of events 23 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	3.6% 30/825 • Number of events 36 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.3% 22/412 • Number of events 27 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Musculoskeletal and connective tissue disorders Back pain	4.9% 20/412 • Number of events 23 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.5% 45/825 • Number of events 45 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.6% 23/412 • Number of events 29 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Nervous system disorders Dizziness	2.4% 10/412 • Number of events 14 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	2.9% 24/825 • Number of events 30 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	5.3% 22/412 • Number of events 25 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.
Nervous system disorders Headache	10.9% 45/412 • Number of events 143 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	12.8% 106/825 • Number of events 207 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.	14.6% 60/412 • Number of events 100 • Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised treatment. The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators.

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER