The Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Obesity
Interventions:	Drug: liraglutide Drug: orlistat Drug: placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
19 sites in 8 countries: Denmark (3), Sweden (2), Finland (3), UK (3), Netherlands (1), Belgium (1), Spain (4) and Czech Republic (2)

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Between screening and randomisation, eligible subjects were included in a 2-week single-blind run-in period in which all subjects were placed on a hypocaloric diet. The dose of liraglutide and placebo was increased during the first 4 weeks after randomisation until maintenance dose was reached. Orlistat dose was fixed from randomisation.

Reporting Groups

	Description
Lira Placebo/Lira 2.4 mg/Lira 3.0 mg	Liraglutide placebo once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 1.2 mg/Lira 3.0 mg	Liraglutide 1.2 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 1.8 mg/Lira 3.0 mg	Liraglutide 1.8 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 2.4 mg/Lira 3.0 mg	Liraglutide 2.4 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Liraglutide 3.0 mg	Liraglutide 3.0 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Orlistat	Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal, weeks 0-20 (open-label) continued to receive Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal in open-label extension period (weeks 20-104)

Participant Flow for 2 periods

Period 1: Double-Blind, Week 0-20

	Lira Placebo/Lira 2.4 mg/Lira 3.0 mg	Lira 1.2 mg/Lira 3.0 mg	Lira 1.8 mg/Lira 3.0 mg	Lira 2.4 mg/Lira 3.0 mg	Liraglutide 3.0 mg	Orlistat
STARTED	98	95	90	93	93	95
COMPLETED	79	85	74	73	82	79
NOT COMPLETED	19	10	16	20	11	16
Adverse Event	3	4	5	9	5	3
Protocol Violation	3	2	2	3	2	2
Lack of Efficacy	2	1	1	0	0	1
Other	11	3	8	8	4	10

Period 2: Open-Label Extension, Week 20-104

	Lira Placebo/Lira 2.4 mg/Lira 3.0 mg	Lira 1.2 mg/Lira 3.0 mg	Lira 1.8 mg/Lira 3.0 mg	Lira 2.4 mg/Lira 3.0 mg	Liraglutide 3.0 mg	Orlistat
STARTED	79	85	74	73	82	79
Enrolled in Extension	67	68	59	65	72	67
COMPLETED	47	46	38	45	47	45
NOT COMPLETED	32	39	36	28	35	34
Not giving consent for extension	12	17	15	8	10	12
Adverse Event	3	4	7	4	4	0
Protocol Violation	1	2	3	1	5	3
Lack of Efficacy	3	2	5	2	0	1
Other	13	14	6	13	16	18

Baseline Characteristics

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Reporting Groups

	Description
Lira Placebo/Lira 2.4 mg/Lira 3.0 mg	Liraglutide placebo once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 1.2 mg/Lira 3.0 mg	Liraglutide 1.2 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 1.8 mg/Lira 3.0 mg	Liraglutide 1.8 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Lira 2.4 mg/Lira 3.0 mg	Liraglutide 2.4 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Liraglutide 3.0 mg	Liraglutide 3.0 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)
Orlistat	Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal, weeks 0-20 (open-label) continued to receive Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal in open-label extension period (weeks 20-104)

Baseline Measures

	Lira Placebo/Lira 2.4 mg/Lira 3.0 mg	Lira 1.2 mg/Lira 3.0 mg	Lira 1.8 mg/Lira 3.0 mg	Lira 2.4 mg/Lira 3.0 mg	Liraglutide 3.0 mg	Orlistat	Total
Number of Participants [units: participants]	98	95	90	93	93	95	564
Age [units: years] Mean ± Standard Deviation	45.86 ± 10.28	47.18 ± 9.72	45.53 ± 10.9	45.01 ± 11.09	45.91 ± 10.71	45.94 ± 9.11	45.91 ± 10.29
Gender [units: participants]
Female	74	73	68	71	70	73	429
Male	24	22	22	22	23	22	135
Race/Ethnicity, Customized [units: participants]
White	97	94	88	91	92	93	555
American Indian/Alaska Native	0	0	0	0	0	1	1
Black/African American	1	0	2	1	1	1	6
Other	0	1	0	1	0	0	2
BMI ^[1] [units: kg/m^2] Mean ± Standard Deviation	34.9 ± 2.8	34.8 ± 2.6	35.0 ± 2.6	35.0 ± 2.8	34.8 ± 2.8	34.1 ± 2.6	34.8 ± 2.7
Weight [units: kg] Mean ± Standard Deviation	97.3 ± 12.3	96.2 ± 13.5	98.0 ± 12.5	98.4 ± 13.0	97.6 ± 13.7	96.0 ± 11.7	97.2 ± 12.8
Waist circumference [units: cm] Mean ± Standard Deviation	108.3 ± 10.0	108.8 ± 10.4	108.2 ± 9.5	110.2 ± 10.7	108.9 ± 8.3	107.6 ± 9.7	108.7 ± 9.8
HbA1c ^[2] [units: percentage (%) of total haemoglobin] Mean ± Standard Deviation	5.60 ± 0.38	5.58 ± 0.33	5.60 ± 0.40	5.54 ± 0.33	5.57 ± 0.40	5.55 ± 0.32	5.60 ± 0.4
Blood pressure [units: mmHg] Mean ± Standard Deviation
Systolic	123.6 ± 11.1	127.0 ± 13.1	123.4 ± 13.0	126.2 ± 13.9	124.3 ± 11.3	122.7 ± 13.5	124.5 ± 12.7
Diastolic	76.8 ± 8.5	79.7 ± 9.1	77.9 ± 7.9	78.6 ± 8.2	77.8 ± 8.3	76.9 ± 7.9	77.9 ± 8.4

[1]	BMI = Body Mass Index
[2]	HbA1c = glycosylated haemoglobin A1c

Outcome Measures

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1. Primary:

Mean Change From Baseline in Body Weight at Week 20 [ Time Frame: Week 0, week 20 ]

Show Outcome Measure 1

2. Secondary:

Mean Change From Baseline in Body Weight at Week 104 [ Time Frame: Week 0, week 104 ]

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3. Secondary:

Change From Baseline in Fasting Plasma Glucose at Week 20 [ Time Frame: Week 0, week 20 ]

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4. Secondary:

Change From Baseline in Fasting Plasma Glucose at Week 104 [ Time Frame: Week 0, week 104 ]

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5. Secondary:

Change From Baseline in Fasting Insulin at Week 20 [ Time Frame: Week 0, week 20 ]

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6. Secondary:

Change From Baseline in Fasting Insulin at Week 104 [ Time Frame: Week 0, week 104 ]

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7. Secondary:

Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 20 [ Time Frame: Week 0, week 20 ]

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8. Secondary:

Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 104 [ Time Frame: Week 0, week 104 ]

Show Outcome Measure 8

9. Secondary:

Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 20 [ Time Frame: Week 0, week 20 ]

Show Outcome Measure 9

10. Secondary:

Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 104 [ Time Frame: Week 0, week 104 ]

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11. Secondary:

Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 20 [ Time Frame: Week 0, week 20 ]

Show Outcome Measure 11

12. Secondary:

Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 104 [ Time Frame: Week 0, week 104 ]

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13. Secondary:

Change From Baseline in Fibrinogen at Week 20 [ Time Frame: Week 0, week 20 ]

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14. Secondary:

Change From Baseline in Fibrinogen at Week 104 [ Time Frame: Week 0, week 104 ]

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15. Secondary:

Change From Baseline in Adiponectin at Week 20 [ Time Frame: Week 0, week 20 ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in Adiponectin at Week 104 [ Time Frame: Week 0, week 104 ]

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17. Secondary:

Change From Baseline in Waist Circumference at Week 20 [ Time Frame: Week 0, week 20 ]

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18. Secondary:

Change From Baseline in Waist Circumference at Week 104 [ Time Frame: Week 0, week 104 ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in Blood Pressure at Week 20 [ Time Frame: Week 0, week 20 ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in Blood Pressure at Week 104 [ Time Frame: Week 0, week 104 ]

Show Outcome Measure 20

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Novo Nordisk acknowledges the Investigator’s right to publish the entire results of the trial. Any such scientific paper, presentation, communication or other information concerning the investigation described in this protocol, must be submitted in writing to Novo Nordisk’s Trial Manager prior to submission for publication/presentation for comments. Comments will be given within four weeks from receipt of the manuscript.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com

No publications provided by Novo Nordisk

Publications automatically indexed to this study:

Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Nov 7;374(9701):1606-16. Epub 2009 Oct 23.

Responsible Party:	Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier:	NCT00422058 History of Changes
Obsolete Identifiers:	NCT00480909
Other Study ID Numbers:	NN8022-1807, 2006-004481-13
Study First Received:	January 12, 2007
Results First Received:	April 27, 2010
Last Updated:	February 14, 2011
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory; Denmark: Danish Medicines Agency; Finland: Finnish Medicines Agency; Czech Republic: State Institute for Drug Control; Spain: Spanish Agency for Medicines; Belgium: FPS of Public Health, Directorate General for the protection of Public Health: Medicines; Sweden: Medical Products Agency; Netherlands: Medicines Evaluation Board, Dutch Health Care Inspectorate