Clinical trial NCT01272232: Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE™ - Diabetes
Official title: Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: A 56 Week Randomised, Double-blind, Placebo-controlled, Three Armed Parallel Group, Multi-centre, Multinational Trial With a 12 Week Observational Follow-up Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolism and Nutrition Disorder
Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2011-01-07
Enrollment: 846
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia, Europe and the United States of America (USA).

The aim of this trial is to investigate the potential of liraglutide to induce and maintain weight loss in overweight or obese subjects with type 2 diabetes. Treatment will be added onto subject's pre-trial background diabetes treatment of either diet and exercise only or single compound oral antidiabetic drug (OAD) treatment (metformin, sulphonylurea \[SU\] or glitazone) or combination OAD treatment (metformin, sulphonylurea or glitazone). The duration of the trial will be 56 weeks followed by a 12 week observational follow-up period.


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained
* Subjects diagnosed with type 2 diabetes and treated with either diet and exercise alone, metformin, sulphonylurea, glitazone as single agent therapy or a combination of the previously mentioned compounds
* HbA1c 7.0-10.0% (both inclusive)
* Body Mass Index (BMI) at least 27.0 kg/m\^2
* Stable body weight
* Preceding failed dietary effort

Exclusion Criteria:

* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors or insulin within the last 3 months
* Known proliferative retinopathy or maculopathy
* History of acute or chronic pancreatitis
* Obesity induced by drug treatment
* Use of approved weight lowering pharmacotherapy
* Previous surgical treatment of obesity
* History of major depressive disorder or suicide attempt
* Uncontrolled hypertension (systolic blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg)
* Screening calcitonin of 50 ng/L or above
* Familial or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
* Personal history of non-familial medullary thyroid carcinoma

Primary outcomes:
measure: Change (%) From Baseline in Body Weight (Fasting)
timeFrame: Week 0, week 56
measure: Proportion of Subjects Losing at Least 5% of Baseline Body Weight
timeFrame: at 56 weeks
measure: Proportion of Subjects Losing More Than 10% of Baseline Body Weight
timeFrame: at 56 weeks
Secondary outcomes:
measure: Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c)
timeFrame: Week 0, week 56
measure: Proportion of Subjects Reaching Target HbA1c Below 7%
timeFrame: at 56 weeks
measure: Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5%
timeFrame: at 56 weeks
measure: Change From Baseline in Waist Circumference
timeFrame: Week 0, week 56
measure: Change (%) From Baseline in Body Weight (Fasting)
timeFrame: Week 0, week 68
measure: Change (%) From Week 56 to 68 in Body Weight (Fasting)
timeFrame: Week 56, week 68
measure: Change From Baseline in Waist Circumference
timeFrame: Week 0, week 68
measure: Change From Week 56 to 68 in Waist Circumference
timeFrame: Week 56, week 68
measure: Incidence of Hypoglycaemic Episodes
timeFrame: Weeks 0-56
Other outcomes:
Locations:
city: Vestavia Hills
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Peoria
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Jonesboro
country: United States
facility: Novo Nordisk Investigational Site
state: Arkansas
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Long Beach
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Mission Hills
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Arvada
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Brooksville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Kissimmee
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Plantation
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Novo Nordisk Investigational Site
state: Hawaii
city: Meridian
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
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state: Kentucky
city: Louisville
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facility: Novo Nordisk Investigational Site
state: Kentucky
city: New Orleans
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facility: Novo Nordisk Investigational Site
state: Louisiana
city: Columbia
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Southfield
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Toms River
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Endwell
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Morehead City
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Anderson
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Moncks Corner
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Bristol
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Saint George
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Newport News
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Bondy
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Le Creusot
country: France
facility: Novo Nordisk Investigational Site
city: Nanterre
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: Pointe À Pitre
country: France
facility: Novo Nordisk Investigational Site
city: Saint Herblain
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Gebhardshain
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Heidelberg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Münster
country: Germany
facility: Novo Nordisk Investigational Site
city: Schkeuditz
country: Germany
facility: Novo Nordisk Investigational Site
city: Stuttgart
country: Germany
facility: Novo Nordisk Investigational Site
city: Wangen
country: Germany
facility: Novo Nordisk Investigational Site
city: Jaipur
country: India
facility: Novo Nordisk Investigational Site
state: Rajasthan
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Pune
country: India
facility: Novo Nordisk Investigational Site
city: Thriruvananthapuram
country: India
facility: Novo Nordisk Investigational Site
city: Beer Sheva
country: Israel
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Jerusalem
country: Israel
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city: Rishon Le Zion
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Catanzaro
country: Italy
facility: Novo Nordisk Investigational Site
city: Chieti Scalo
country: Italy
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Forlì
country: Italy
facility: Novo Nordisk Investigational Site
city: Latina
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Padova
country: Italy
facility: Novo Nordisk Investigational Site
city: Perugia
country: Italy
facility: Novo Nordisk Investigational Site
city: Pistoia
country: Italy
facility: Novo Nordisk Investigational Site
city: San Juan
country: Puerto Rico
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city: Port Elizabeth
country: South Africa
facility: Novo Nordisk Investigational Site
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Novo Nordisk Investigational Site
state: Free State
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Lenasia
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Brits
country: South Africa
facility: Novo Nordisk Investigational Site
state: North West
city: Cape Town
country: South Africa
facility: Novo Nordisk Investigational Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Novo Nordisk Investigational Site
state: Western Cape
city: Granada
country: Spain
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Palma de Mallorca
country: Spain
facility: Novo Nordisk Investigational Site
city: Partida De Bacarot
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Dalby
country: Sweden
facility: Novo Nordisk Investigational Site
city: Göteborg
country: Sweden
facility: Novo Nordisk Investigational Site
city: Göteborg
country: Sweden
facility: Novo Nordisk Investigational Site
city: Luleå
country: Sweden
facility: Novo Nordisk Investigational Site
city: Lund
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Ängelholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Örebro
country: Sweden
facility: Novo Nordisk Investigational Site
city: Taichung
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Tainan city
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taoyuan
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Gaziantep
country: Turkey
facility: Novo Nordisk Investigational Site
city: Hatay
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Izmir
country: Turkey
facility: Novo Nordisk Investigational Site
city: Kahramanmaras
country: Turkey
facility: Novo Nordisk Investigational Site
city: Airdrie
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Ayr
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bexhill-on-Sea
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Birmingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bristol
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Cambridge
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Chester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Darlington
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Leeds
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Leicester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Middlesbrough
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Nottingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Plymouth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rotherham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Swansea
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Truro
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: le Roux C, Aroda V, Hemmingsson J, Cancino AP, Christensen R, Pi-Sunyer X. Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m(2): A Post-hoc Analysis. Obes Facts. 2017;10(6):531-544. doi: 10.1159/000478099. Epub 2017 Nov 17.
citation: Overgaard RV, Petri KC, Jacobsen LV, Jensen CB. Liraglutide 3.0 mg for Weight Management: A Population Pharmacokinetic Analysis. Clin Pharmacokinet. 2016 Nov;55(11):1413-1422. doi: 10.1007/s40262-016-0410-7.
citation: O'Neil PM, Garvey WT, Gonzalez-Campoy JM, Mora P, Ortiz RV, Guerrero G, Claudius B, Pi-Sunyer X; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. EFFECTS OF LIRAGLUTIDE 3.0 MG ON WEIGHT AND RISK FACTORS IN HISPANIC VERSUS NON-HIPANIC POPULATIONS: SUBGROUP ANALYSIS FROM SCALE RANDOMIZED TRIALS. Endocr Pract. 2016 Nov;22(11):1277-1287. doi: 10.4158/EP151181.OR. Epub 2016 Aug 2.
citation: Fujioka K, O'Neil PM, Davies M, Greenway F, C W Lau D, Claudius B, Skjoth TV, Bjorn Jensen C, P H Wilding J. Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers. Obesity (Silver Spring). 2016 Nov;24(11):2278-2288. doi: 10.1002/oby.21629.
citation: Bays H, Pi-Sunyer X, Hemmingsson JU, Claudius B, Jensen CB, Van Gaal L. Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects. Curr Med Res Opin. 2017 Feb;33(2):225-229. doi: 10.1080/03007995.2016.1251892. Epub 2016 Nov 6.
citation: Ard J, Cannon A, Lewis CE, Lofton H, Vang Skjoth T, Stevenin B, Pi-Sunyer X. Efficacy and safety of liraglutide 3.0 mg for weight management are similar across races: subgroup analysis across the SCALE and phase II randomized trials. Diabetes Obes Metab. 2016 Apr;18(4):430-5. doi: 10.1111/dom.12632. Epub 2016 Feb 11.
citation: Wilding JP, Overgaard RV, Jacobsen LV, Jensen CB, le Roux CW. Exposure-response analyses of liraglutide 3.0 mg for weight management. Diabetes Obes Metab. 2016 May;18(5):491-9. doi: 10.1111/dom.12639. Epub 2016 Mar 1.
citation: Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjoth TV, Andreasen AH, Jensen CB, DeFronzo RA; NN8022-1922 Study Group. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015 Aug 18;314(7):687-99. doi: 10.1001/jama.2015.9676.
citation: McEvoy BW. Missing data in clinical trials for weight management. J Biopharm Stat. 2016;26(1):30-6. doi: 10.1080/10543406.2015.1094814.
citation: 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.
citation: von Scholten BJ, Davies MJ, Persson F, Hansen TW, Madsbad S, Endahl L, Jepsen CH, Rossing P. Effect of weight reductions on estimated kidney function: Post-hoc analysis of two randomized trials. J Diabetes Complications. 2017 Jul;31(7):1164-1168. doi: 10.1016/j.jdiacomp.2017.04.003. Epub 2017 Apr 11.
citation: 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.
citation: 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.