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

Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes: A 20-week Randomised, Double-blind, Placebo-controlled, Six Armed Parallel Group, Multi-centre, Multinational Trial With an Open Label Orlistat Comparator Arm and With an 84-week Extension Period

This trial is conducted in Europe. The purpose of the 20-week trial is to investigate the efficacy of liraglutide to induce body weight loss and the purpose of the extension is to evaluate the long term safety and tolerability of liraglutide.

Trial has the following trial periods: A 20-week randomised, double-blind, placebo-controlled, six-armed parallel-group, multi-centre, multinational trial with an open label orlistat comparator arm followed by an 84 week extension period.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolism and Nutrition Disorder
• Intervention / Treatment: Drug: placebo; Drug: liraglutide; Drug: orlistat

• Study Type: Interventional
• Enrollment (Actual): 564
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Novo Nordisk Investigational Site
• Czechia
  • Praha 1, Czechia, 116 94
    • Novo Nordisk Investigational Site
  • Praha 2, Czechia, 128 08
    • Novo Nordisk Investigational Site
• Denmark
  • Frederiksberg C, Denmark, 1958
    • Novo Nordisk Investigational Site
  • Hvidovre, Denmark, 2650
    • Novo Nordisk Investigational Site
  • Århus C, Denmark, 8000
    • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00270
    • Novo Nordisk Investigational Site
  • Kuopio, Finland, 70210
    • Novo Nordisk Investigational Site
  • Oulu, Finland, 90220
    • Novo Nordisk Investigational Site
• Netherlands
  • Almere, Netherlands, 1311RL
    • Novo Nordisk Investigational Site
• Spain
  • Barcelona, Spain, 08022
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28006
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28007
    • Novo Nordisk Investigational Site
  • Pamplona, Spain, 31008
    • Novo Nordisk Investigational Site
• Sweden
  • Malmö, Sweden, 205 02
    • Novo Nordisk Investigational Site
  • Stockholm, Sweden, 141 86
    • Novo Nordisk Investigational Site
• United Kingdom
  • Glasgow, United Kingdom, G322ER
    • Novo Nordisk Investigational Site
  • Luton, United Kingdom, LU4 0DZ
    • Novo Nordisk Investigational Site
  • Norwich, United Kingdom, NR4 7TJ
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index (BMI) greater than or equal to 30.0 or lesser than or equal to 40.0 kg/m2
• Stable body weight (less than 5% selfreported change within the last 3 months)

Exclusion Criteria:

• Obesity induced by drug treatment
• Use of approved drugs for weight lowering intervention (e.g. orlistat, sibutramin, rimonabant) within the last 3 months prior to entering trial
• Type 1 or type 2 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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)	Drug: placebo; Injected s.c. (under the skin) once daily
Experimental: 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)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: 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)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: 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)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: 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)	Drug: placebo; Injected s.c. (under the skin) once daily; Drug: liraglutide; Injected s.c. (under the skin) once daily
Active Comparator: 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)	Drug: orlistat; 120 mg capsule. Administered thrice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Body Weight at Week 20	Calculated as mean body weight at week 20 - baseline	Week 0, week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Body Weight at Week 104	Calculated as mean body weight at week 104 - baseline	Week 0, week 104
Change From Baseline in Fasting Plasma Glucose at Week 20	Calculated as mean fasting plasma glucose at week 20 - baseline	Week 0, week 20
Change From Baseline in Fasting Plasma Glucose at Week 104	Calculated as mean fasting plasma glucose at week 104 - baseline	Week 0, week 104
Change From Baseline in Fasting Insulin at Week 20	Calculated as mean fasting insulin at week 20 - baseline	Week 0, week 20
Change From Baseline in Fasting Insulin at Week 104	Calculated as mean fasting insulin at week 104 - baseline	Week 0, week 104
Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 20	Calculated as mean HbA1c (glycosylated haemoglobin A1c) at week 20 - baseline	Week 0, week 20
Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 104	Calculated as mean HbA1c (glycosylated haemoglobin A1c) at week 104 - baseline	Week 0, week 104
Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 20	Calculated as mean hsCRP (highly sensitive C-reactive protein) at week 20-baseline. High hsCRP level is associated with greater cardiovascular risk	Week 0, week 20
Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 104	Calculated as mean hsCRP (highly sensitive C-reactive protein) at week 104- baseline. High hsCRP level is associated with greater cardiovascular risk	Week 0, week 104
Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 20	Calculated as mean PAI-1 (plasminogen activator inhibitor 1) at week 20-baseline. High PAI-1 is associated with greater cardiovascular risk	Week 0, week 20
Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 104	Calculated as mean PAI-1 (plasminogen activator inhibitor 1) at week 104-baseline. High PAI-1 is associated with greater cardiovascular risk	Week 0, week 104
Change From Baseline in Fibrinogen at Week 20	Calculated as mean fibrinogen at week 20 - baseline. High fibrinogen is associated with greater cardiovascular risk	Week 0, week 20
Change From Baseline in Fibrinogen at Week 104	Calculated as mean fibrinogen at week 104 - baseline. High fibrinogen is associated with greater cardiovascular risk	Week 0, week 104
Change From Baseline in Adiponectin at Week 20	Calculated as mean adiponectin at week 20-baseline. A low adiponectin level is associated with greater cardiovascular risk	Week 0, week 20
Change From Baseline in Adiponectin at Week 104	Calculated as mean adiponectin at week 104-baseline. A low adiponectin level is associated with greater cardiovascular risk	Week 0, week 104
Change From Baseline in Waist Circumference at Week 20	Calculated as mean waist circumference at week 20-baseline.	Week 0, week 20
Change From Baseline in Waist Circumference at Week 104	Calculated as mean waist circumference at week 104-baseline.	Week 0, week 104
Change From Baseline in Blood Pressure at Week 20	Calculated as mean blood pressure at week 20-baseline.	Week 0, week 20
Change From Baseline in Blood Pressure at Week 104	Calculated as mean blood pressure at week 104-baseline.	Week 0, week 104

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Steinberg WM, Rosenstock J, Wadden TA, Donsmark M, Jensen CB, DeVries JH. Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program. Diabetes Care. 2017 Jul;40(7):839-848. doi: 10.2337/dc16-2684. Epub 2017 May 4. Erratum In: Diabetes Care. 2018 Jul;41(7):1538.
• O'Neil PM, Aroda VR, Astrup A, Kushner R, Lau DCW, Wadden TA, Brett J, Cancino AP, Wilding JPH; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials. Diabetes Obes Metab. 2017 Nov;19(11):1529-1536. doi: 10.1111/dom.12963. Epub 2017 Jul 21.
• Davies MJ, Aronne LJ, Caterson ID, Thomsen AB, Jacobsen PB, Marso SP; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Liraglutide and cardiovascular outcomes in adults with overweight or obesity: A post hoc analysis from SCALE randomized controlled trials. Diabetes Obes Metab. 2018 Mar;20(3):734-739. doi: 10.1111/dom.13125. Epub 2017 Nov 1.
• Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rossner S, Savolainen MJ, Van Gaal L; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158. Epub 2011 Aug 16. Erratum In: Int J Obes (Lond). 2012 Jun;36(6):890. Int J Obes (Lond). 2013 Feb;37(2):322.
• Astrup A, Rossner 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. doi: 10.1016/S0140-6736(09)61375-1. Epub 2009 Oct 23. Erratum In: Lancet. 2010 Mar 20;375(9719):984.
• Lean ME, Carraro R, Finer N, Hartvig H, Lindegaard ML, Rossner S, Van Gaal L, Astrup A; NN8022-1807 Investigators. Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults. Int J Obes (Lond). 2014 May;38(5):689-97. doi: 10.1038/ijo.2013.149. Epub 2013 Aug 14.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2007
• Primary Completion (Actual): September 13, 2007
• Study Completion (Actual): April 30, 2009

Study Registration Dates

• First Submitted: January 12, 2007
• First Submitted That Met QC Criteria: January 12, 2007
• First Posted (Estimate): January 15, 2007

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: September 29, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Nutrition Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Lipid Regulating Agents; Anti-Obesity Agents; Incretins; Liraglutide; Orlistat
• Other Study ID Numbers: NN8022-1807; 2006-004481-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No