Impact of Liraglutide 3.0 on Body Fat Distribution

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03038620
• Collaborator: Novo Nordisk A/S (Industry)
• Enrollment: 235
• Location: 1
• Arms: 2
• Actual Duration (Months): 45.4
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

This study is a clinical study to investigate the efficacy of liraglutide compared to placebo in reducing visceral adiposity measured by MRI in overweight or obese subjects at high risk for cardiovascular disease after 40 weeks on-treatment.

Condition or Disease	Intervention/Treatment	Phase
Obesity, Visceral; Cardiovascular Diseases; Fat Disorder	Drug: Liraglutide; Drug: Placebo	Phase 4

Detailed Description

Obesity has long been recognized as a risk factor for all-cause mortality and morbidity, including the development of cardiovascular and metabolic diseases such as coronary artery disease, hypertension, insulin resistance, diabetes, and dyslipidemia. Obesity has recently been formally defined as a chronic disease characterized by pathophysiological processes that result in increased adipose tissue mass and can result in increased morbidity and mortality. Although the health risks associated with obesity are clear, there is an emerging appreciation that obesity per se, as defined by simple anthropometric measures such as waist circumference or body mass index (BMI), is neither necessary nor sufficient to promote cardiometabolic disease and atherosclerotic cardiovascular disease (ASCVD) risk. As a result, BMI alone is an insufficient marker of risk and may not accurately identify individuals at elevated risk for ASCVD. There is a pressing need to more accurately phenotype obesity to identify individuals at elevated risk for ASCVD that may benefit from more intensive preventive and therapeutic strategies

Study Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Impact of Liraglutide 3.0 on Body Fat Distribution, Visceral Adiposity, and Cardiometabolic Risk Markers In Overweight and Obese Adults at High Risk for Cardiovascular Disease
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Oct 13, 2020
• Actual Study Completion Date: Oct 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liraglutide 3.0 mg Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection.	Drug: Liraglutide; Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.; Other Names: Saxenda
Placebo Comparator: Placebo Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection.	Drug: Placebo; Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.; Other Names: Saline injection

Outcome Measures

Primary Outcome Measures

1. Relative Percent Reduction in Visceral Adipose Tissue Mass Measured by MRI [Baseline, 40 weeks]

   The effect on relative percent reduction from baseline in visceral adipose tissue mass measured by MRI after 40 weeks on treatment. Positive numbers reflect the reduction in the value from baseline to study endpoint as a percent of the baseline. Reduction in this variable is believed to be associated with lower cardiovascular risk.

Secondary Outcome Measures

1. Absolute Reduction in Visceral Adipose Tissue Volume [Baseline, 40 weeks]

   The effect on absolute reduction from baseline in visceral adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

2. Relative Percent Reduction in Body Weight [Baseline, 40 weeks]

   The effect on relative percent reduction from baseline in body weight after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

3. Absolute Reduction in Body Weight [Baseline, 40 weeks]

   The effect on absolute reduction from baseline in body weight after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

4. Relative Percent Reduction in Waist Circumference [Baseline, 40 weeks]

   The effect on relative percent reduction from baseline in waist circumference after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

5. Absolute Reduction in Waist Circumference [Baseline, 40 weeks]

   The effect on absolute reduction from baseline in waist circumference after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

6. Relative Percent Reduction in Total Body Adipose Tissue [Baseline, 40 weeks]

   The effect on relative percent reduction from baseline in total body adipose tissue (fat) mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

7. Absolute Reduction in Total Body Adipose Tissue [Baseline, 40 weeks]

   The effect on absolute reduction from baseline in total body adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

8. Relative Percent Reduction in Abdominal Subcutaneous Adipose Tissue [Baseline, 40 weeks]

   The effect on relative percent reduction from baseline in abdominal subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

9. Absolute Reduction in Abdominal Subcutaneous Adipose Tissue [Baseline, 40 weeks]

   The effect on absolute reduction from baseline in abdominal subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

10. Relative Percent Reduction in Lower Body Subcutaneous Adipose Tissue [Baseline, 40 weeks]

    The effect on relative percent reduction from baseline in lower body subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

11. Absolute Reduction in Lower Body Subcutaneous Adipose Tissue [Baseline, 40 weeks]

    The effect on absolute reduction from baseline in lower body subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

12. Relative Percent Reduction in Liver Fat Percent [Baseline, 40 weeks]

    The effect on relative percent reduction from baseline in liver (hepatic) fat percentage measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

13. Absolute Reduction in Liver Fat Percent [Baseline, 40 weeks]

    The effect on absolute reduction from baseline in liver (hepatic) fat percentage measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.

14. Relative Percent Reduction in Total Body Lean Volume [Baseline, 40 weeks]

    The effect on relative percent reduction from baseline in total body lean volume (fat-free mass) measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

15. Absolute Reduction in Total Body Lean Volume [Baseline, 40 weeks]

    The effect on absolute reduction from baseline in total body lean volume (fat-free mass) measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

16. Relative Percent Reduction in Total Thigh Muscle Volume [Baseline, 40 weeks]

    The effect on relative percent reduction from baseline in total thigh muscle volume measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

17. Absolute Reduction in Total Thigh Muscle Volume [Baseline, 40 weeks]

    The effect on absolute reduction from baseline in total thigh muscle volume measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.

18. Relative Percent Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent [Baseline,40 weeks]

    The effect on relative percent reduction from baseline in mean anterior thigh muscle fat infiltration percent measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower risk for metabolic disease.

19. Absolute Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent [Baseline,40 weeks]

    The effect on absolute reduction from baseline in mean anterior thigh muscle fat infiltration percent measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower risk for metabolic disease

20. Change From Baseline in VAT/SAT Ratio [Baseline, 40 weeks]

    The effect on absolute reduction from baseline in Visceral adipose tissue/subcutaneous adipose tissue (VAT/SAT) ratio measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. This is the ratio of visceral adipose tissue to subcutaneous adipose tissue and it is thought that lower values (relatively less visceral adipose tissue) are better.

21. Change From Baseline in Total Fat/Fat-free Mass Ratio [Baseline, 40 weeks]

    The effect on absolute change from baseline in total fat/fat-free mass ratio measured by MRI after 40 weeks on treatment versus placebo. This is a ratio of fat to lean mass and it is believed that lower values (less fat relative to lean mass) is better.

22. Relative Percent Change in Fasting Blood Glucose [Baseline, 40 weeks]

    The relative percent change in fasting blood glucose from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a reduction. This is a blood based biomarker for diabetes in which normal levels are desirable (70-100 mg/dL).

23. Relative Percent Change in Insulin [Baseline, 40 weeks]

    The relative percent change in insulin from baseline to study end point as a percent of baseline by treatment group. Positive values reflect an increase. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. This is a blood based biomarker in which lower fasting levels are desirable.

24. Relative Percent Change in HOMA-IR [Baseline, 40 weeks]

    The relative percent change in HOMA-IR from baseline to study end point as a percent of baseline by treatment group. Positive values reflect an increase. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. The relative percent change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline to study end point by treatment group measures insulin resistance. Levels above 1.9 signal early insulin resistance, while levels above 2.9 signal significant insulin resistance. There will be optimal insulin sensitivity if HOMA-IR is less than 1.

25. Relative Percent Change in C-reactive Protein [Baseline, 40 weeks]

    The relative percent change in biomarker of inflammation: C-reactive protein (CRP) from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. This is a blood based test for which lower values are associated with less inflammation and lower risk for cardiovascular events.

26. Relative Percent Change in Triglyceride/HDL-C Ratio [Baseline, 40 weeks]

    The relative percent change in triglyceride/HDL-C ratio from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. Lower ratio of triglycerides to HDL-cholesterol is associated with less insulin resistance and lower cardiovascular risk.

27. Relative Percent Change in Nt-proBNP [Baseline, 40 weeks]

    The relative percent change in N-terminal Pro Brain Natriuretic Peptides (Nt-proBNP) from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. NT-proBNP is a blood based biomarker. Lower levels are associated with lower risk for heart failure and cardiovascular events.

28. Absolute Change in Fasting Blood Glucose [Baseline,40 weeks]

    The change in fasting blood glucose from baseline to study end point by treatment group.

29. Absolute Change in Insulin [Baseline, 40 weeks]

    The absolute change in insulin from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits.

30. Absolute Change in HOMA-IR [Baseline, 40 weeks]

    The absolute change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline to study end point by treatment group measures insulin resistance. Levels above 1.9 signal early insulin resistance, while levels above 2.9 signal significant insulin resistance. There will be optimal insulin sensitivity if HOMA-IR is less than 1. Collection was impacted by COVID-19 and changes to study visits.

31. Absolute Change in CRP [Baseline, 40 weeks]

    The change in Markers of inflammation: C-reactive protein (CRP) from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. This is a blood based test for which lower values are associated with less inflammation and lower risk for cardiovascular events.

32. Absolute Change in Triglyceride/HDL-C Ratio [Baseline, 40 weeks]

    The change in triglyceride/HDL-C ratio from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. Lower ratio of triglycerides to HDL-cholesterol is associated with less insulin resistance and lower cardiovascular risk.

33. Absolute Change in Nt-proBNP [Baseline, 40 weeks]

    The change in N-terminal Pro Brain Natriuretic Peptides (Nt-proBNP) from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. NT-proBNP is a blood based biomarker. Lower levels are associated with lower risk for heart failure and cardiovascular events.

34. Change From Baseline in Heart Rate [Baseline, 40 weeks]

    The change in heart rate/pulse from baseline to study endpoint visit by treatment group.

35. Change From Baseline in Blood Pressure [Baseline, 40 weeks]

    The change in systolic blood pressure from baseline to study endpoint visit by treatment group.

Other Outcome Measures

1. On-treatment Time, Weeks [weeks]

   The mean duration of treatment during study follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age ≥ 35 years

• Able to provide informed consent

• BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with metabolic syndrome

• Metabolic syndrome is defined as at least three of the following:3

1. waist circumference > 102 cm (40 in) in men and 88 cm (35 in) in women

2. triglycerides > 150 mg/dL or on treatment for hypertriglyceridemia

3. HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women

4. blood pressure > 130/85 mmHg or on treatment for hypertension

5. fasting glucose > 100 mg/dL

Exclusion Criteria:

• Treatment with Glucagon-like peptide-1 (GLP-1) receptor agonists (including liraglutide, exenatide or others as they become available), dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin within the last 3 months.

• Receipt of any anti-obesity drug or supplement within 1 month prior to screening for this trial.

• Self-reported or clinically documented history of significant fluctuations (>5% change) in weight within 3 months prior to screening for this trial.

• History of diabetes mellitus (type 1 or 2) or on treatment with anti-diabetes medication.

• History of chronic pancreatitis or idiopathic acute pancreatitis (current or prior history).

• History of gallbladder disease (cholelithiasis or cholecystitis).

• Chronic kidney disease stage III or greater (eGFR<60 mL/min).

• Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome).

• Current or history of treatment with medications that may cause significant weight gain, within 1 month prior to screening for this trial, including systemic corticosteroids (except for a short course of treatment, i.e., 7- 10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine, amitryptiline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium).

• Diet attempts using herbal supplements or over-the-counter medications within 1 month prior to screening for this trial.

• Current participation in an organized weight reduction program or within the last 1 month prior to screening for this trial.

• Participation in a clinical trial within the last 3 months prior to screening for this trial.

• Familial or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma.

• Personal history of non-familial medullary thyroid carcinoma.

• History of Major Depressive Disorder within the last 2 years.

• History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder.

• Any lifetime history of a suicide attempt.

• A history of any suicidal behavior in the last month prior to randomization.

• Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator.

• Known or suspected hypersensitivity to trial product(s) or related product(s).

• Known or suspected abuse of alcohol or narcotics.

• Language barrier, mental incapacity, unwillingness or inability to understand.

• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. These include abstinence and the following methods: diaphragm with spermicide, condom with spermicide (by male partner), intrauterine device, sponge, spermicide, Norplant®, Depo-Provera® or oral contraceptives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• Novo Nordisk A/S

Investigators

• Principal Investigator: Parag Joshi, MD, University of Texas Southwestern Medical Center

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2018
• Statistical Analysis Plan - Jul 28, 2020

More Information

Publications

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• Cerhan JR, Moore SC, Jacobs EJ, Kitahara CM, Rosenberg PS, Adami HO, Ebbert JO, English DR, Gapstur SM, Giles GG, Horn-Ross PL, Park Y, Patel AV, Robien K, Weiderpass E, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hartge P, Bernstein L, Berrington de Gonzalez A. A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. 2014 Mar;89(3):335-45. doi: 10.1016/j.mayocp.2013.11.011.
• Chandra A, Neeland IJ, Berry JD, Ayers CR, Rohatgi A, Das SR, Khera A, McGuire DK, de Lemos JA, Turer AT. The relationship of body mass and fat distribution with incident hypertension: observations from the Dallas Heart Study. J Am Coll Cardiol. 2014 Sep 9;64(10):997-1002. doi: 10.1016/j.jacc.2014.05.057.
• Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodés-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. doi: 10.1161/ATVBAHA.107.159228. Epub 2008 Mar 20. Review. Erratum in: Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):e151.
• Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012 Sep 4;126(10):1301-13. doi: 10.1161/CIRCULATIONAHA.111.067264. Review.
• Dong Z, Luo Y, Zhang Z, Cai H, Li Y, Chan T, Wu L, Li ZP, Feng ST. MR quantification of total liver fat in patients with impaired glucose tolerance and healthy subjects. PLoS One. 2014 Oct 24;9(10):e111283. doi: 10.1371/journal.pone.0111283. eCollection 2014.
• Garvey WT, Garber AJ, Mechanick JI, Bray GA, Dagogo-Jack S, Einhorn D, Grunberger G, Handelsman Y, Hennekens CH, Hurley DL, McGill J, Palumbo P, Umpierrez G; The Aace Obesity Scientific Committee. American association of clinical endocrinologists and american college of endocrinology position statement on the 2014 advanced framework for a new diagnosis of obesity as a chronic disease. Endocr Pract. 2014 Sep;20(9):977-89. doi: 10.4158/EP14280.PS.
• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Fernando Costa. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005 Dec;4(4):198-203.
• Hsu WC, Araneta MR, Kanaya AM, Chiang JL, Fujimoto W. BMI cut points to identify at-risk Asian Americans for type 2 diabetes screening. Diabetes Care. 2015 Jan;38(1):150-8. doi: 10.2337/dc14-2391. Review.
• Human energy requirements: report of a joint FAO/ WHO/UNU Expert Consultation. Food Nutr Bull. 2005 Mar;26(1):166.
• McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011 Nov;96(11):E1756-60. doi: 10.1210/jc.2011-0615. Epub 2011 Aug 24.
• McLaughlin T, Sherman A, Tsao P, Gonzalez O, Yee G, Lamendola C, Reaven GM, Cushman SW. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia. 2007 Aug;50(8):1707-15. Epub 2007 Jun 5.
• Mørkedal B, Vatten LJ, Romundstad PR, Laugsand LE, Janszky I. Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (Nord-Trøndelag Health Study), Norway. J Am Coll Cardiol. 2014 Mar 25;63(11):1071-8. doi: 10.1016/j.jacc.2013.11.035. Epub 2013 Dec 15.
• Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity (Silver Spring). 2013 Sep;21(9):E439-47. doi: 10.1002/oby.20135. Epub 2013 May 19.
• Neeland IJ, Gupta S, Ayers CR, Turer AT, Rame JE, Das SR, Berry JD, Khera A, McGuire DK, Vega GL, Grundy SM, de Lemos JA, Drazner MH. Relation of regional fat distribution to left ventricular structure and function. Circ Cardiovasc Imaging. 2013 Sep;6(5):800-7. doi: 10.1161/CIRCIMAGING.113.000532. Epub 2013 Aug 8.
• Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012 Sep 19;308(11):1150-9.
• Schaudinn A, Linder N, Garnov N, Kerlikowsky F, Blüher M, Dietrich A, Schütz T, Karlas T, Kahn T, Busse H. Predictive accuracy of single- and multi-slice MRI for the estimation of total visceral adipose tissue in overweight to severely obese patients. NMR Biomed. 2015 May;28(5):583-90. doi: 10.1002/nbm.3286. Epub 2015 Mar 25.
• See R, Abdullah SM, McGuire DK, Khera A, Patel MJ, Lindsey JB, Grundy SM, de Lemos JA. The association of differing measures of overweight and obesity with prevalent atherosclerosis: the Dallas Heart Study. J Am Coll Cardiol. 2007 Aug 21;50(8):752-9. Epub 2007 Aug 6.
• Thomas MS, Newman D, Leinhard OD, Kasmai B, Greenwood R, Malcolm PN, Karlsson A, Rosander J, Borga M, Toms AP. Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system. Eur Radiol. 2014 Sep;24(9):2279-91. doi: 10.1007/s00330-014-3226-6. Epub 2014 May 29.
• Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, Aronne L; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013 Nov;37(11):1443-51. doi: 10.1038/ijo.2013.120. Epub 2013 Jul 1. Erratum in: Int J Obes (Lond). 2013 Nov;37(11):1514. Int J Obes (Lond). 2015 Jan;39(1):187.

• Responsible Party: Parag Joshi, M.D., University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03038620
• Other Study ID Numbers: STU 122015-044
• First Posted: Jan 31, 2017
• Last Update Posted: Nov 19, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Parag Joshi, M.D., University of Texas Southwestern Medical Center: Obesity; Visceral; Cardiovascular Disease; Fat
• Additional relevant MeSH terms: Cardiovascular Diseases; Obesity, Abdominal; Liraglutide

Study Results

Participant Flow

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Period Title: Overall Study
STARTED	92	93
COMPLETED	73	55
NOT COMPLETED	19	38

Baseline Characteristics

Arm/Group Title	Liraglutide 3.0 mg	Placebo	Total
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Total of all reporting groups
Overall Participants	73	55	128
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.6 (9.8)	50.9 (8.8)	50.2 (9.4)
Sex: Female, Male (Count of Participants)
Female	67 91.8%	51 92.7%	118 92.2%
Male	6 8.2%	4 7.3%	10 7.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 24.7%	12 21.8%	30 23.4%
Not Hispanic or Latino	55 75.3%	43 78.2%	98 76.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	28 38.4%	19 34.5%	47 36.7%
White	43 58.9%	35 63.6%	78 60.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2.7%	1 1.8%	3 2.3%
Total Adipose tissue (Liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters]	39.6 (8.9)	40.9 (9.8)	40.2 (9.3)
Visceral Adipose Tissue (Liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters]	4.5 (2.1)	4.5 (1.7)	4.5 (1.9)
Abdominal Adipose Tissue (Liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters]	15.6 (4.3)	16.2 (4.2)	15.8 (4.2)
Lower Body Adipose Tissue (Liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters]	14.7 (4.3)	15.6 (5.0)	15.1 (4.6)
Liver Fat (percentage of fat) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of fat]	7.6 (7.9)	6.1 (6.1)	6.9 (7.2)
Total Body Lean Tissue (Liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters]	21.6 (3.8)	21.5 (3.5)	21.5 (3.7)
Fasting Blood Glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	100.6 (12.9)	99.1 (14.4)	100 (13.5)
Fasting Insulin (mIU/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mIU/L]	16.3 (10.8)	18.0 (17.0)	17.0 (13.8)
Triglycerides (mg/dL) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	109.4 (49.7)	118.3 (50.6)	113.2 (50.1)
C-reactive Protein (mg/L) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	8.0 (4.3)	7.8 (6.8)	7.9 (5.6)
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (pg/mL) (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	59.6 (44.1)	63.2 (44.7)	61.1 (44.1)
Number of Participants with Hypertension (Count of Participants)
Count of Participants [Participants]	30 41.1%	20 36.4%	50 39.1%
Number of Participants with Hyperlipidemia (Count of Participants)
Count of Participants [Participants]	15 20.5%	16 29.1%	31 24.2%
Number of Participants with Prediabetes (Count of Participants)
Count of Participants [Participants]	2 2.7%	3 5.5%	5 3.9%
Systolic blood pressure (mmHg) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	130.3 (14.9)	125.8 (13.9)	128.4 (14.6)
Diastolic blood pressure (mmHg) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	80.9 (7.8)	78.5 (8.3)	79.8 (8.1)
Weight (kg) (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	101.0 (17.9)	102.3 (17.9)	101.5 (17.9)
Height (m) (m) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m]	1.6 (0.1)	1.6 (0.1)	1.6 (0.1)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	37.2 (6.0)	38.1 (6.1)	37.6 (6.1)
Waist Circumference (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	105.5 (12.2)	104.8 (10.6)	105.2 (11.5)
Baseline kcal/day (kcal/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kcal/day]	2177 (195)	2196 (189)	2185 (192)

Outcome Measures

1. Primary Outcome

Title	Relative Percent Reduction in Visceral Adipose Tissue Mass Measured by MRI
Description	The effect on relative percent reduction from baseline in visceral adipose tissue mass measured by MRI after 40 weeks on treatment. Positive numbers reflect the reduction in the value from baseline to study endpoint as a percent of the baseline. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed study endpoint assessment (interpretable MRI at baseline and at study end).

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (95% Confidence Interval) [percentage of reduction in VAT]	12.49	1.63

2. Secondary Outcome

Title	Absolute Reduction in Visceral Adipose Tissue Volume
Description	The effect on absolute reduction from baseline in visceral adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	0.53 (0.43)	0.10 (0.53)

3. Secondary Outcome

Title	Relative Percent Reduction in Body Weight
Description	The effect on relative percent reduction from baseline in body weight after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	6.59 (4.80)	1.19 (4.68)

4. Secondary Outcome

Title	Absolute Reduction in Body Weight
Description	The effect on absolute reduction from baseline in body weight after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Kilograms]	6.75 (5.35)	1.3 (4.79)

5. Secondary Outcome

Title	Relative Percent Reduction in Waist Circumference
Description	The effect on relative percent reduction from baseline in waist circumference after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	6.90 (6.43)	4.16 (6.06)

6. Secondary Outcome

Title	Absolute Reduction in Waist Circumference
Description	The effect on absolute reduction from baseline in waist circumference after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [cm]	7.4 (6.8)	4.6 (6.7)

7. Secondary Outcome

Title	Relative Percent Reduction in Total Body Adipose Tissue
Description	The effect on relative percent reduction from baseline in total body adipose tissue (fat) mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	9.59 (7.15)	0.95 (7.80)

8. Secondary Outcome

Title	Absolute Reduction in Total Body Adipose Tissue
Description	The effect on absolute reduction from baseline in total body adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	3.76 (2.87)	0.42 (2.92)

9. Secondary Outcome

Title	Relative Percent Reduction in Abdominal Subcutaneous Adipose Tissue
Description	The effect on relative percent reduction from baseline in abdominal subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	9.87 (8.23)	0.77 (8.40)

10. Secondary Outcome

Title	Absolute Reduction in Abdominal Subcutaneous Adipose Tissue
Description	The effect on absolute reduction from baseline in abdominal subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	1.52 (1.31)	0.15 (1.24)

11. Secondary Outcome

Title	Relative Percent Reduction in Lower Body Subcutaneous Adipose Tissue
Description	The effect on relative percent reduction from baseline in lower body subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	9.95 (7.61)	1.29 (8.57)

12. Secondary Outcome

Title	Absolute Reduction in Lower Body Subcutaneous Adipose Tissue
Description	The effect on absolute reduction from baseline in lower body subcutaneous adipose tissue mass measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	1.51 (1.34)	0.19 (1.19)

13. Secondary Outcome

Title	Relative Percent Reduction in Liver Fat Percent
Description	The effect on relative percent reduction from baseline in liver (hepatic) fat percentage measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	12.37 (61.43)	-20.63 (104.92)

14. Secondary Outcome

Title	Absolute Reduction in Liver Fat Percent
Description	The effect on absolute reduction from baseline in liver (hepatic) fat percentage measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percentage of liver fat]	2.35 (5.35)	-0.01 (3.24)

15. Secondary Outcome

Title	Relative Percent Reduction in Total Body Lean Volume
Description	The effect on relative percent reduction from baseline in total body lean volume (fat-free mass) measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	2.47 (4.04)	0.90 (3.66)

16. Secondary Outcome

Title	Absolute Reduction in Total Body Lean Volume
Description	The effect on absolute reduction from baseline in total body lean volume (fat-free mass) measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	0.54 (0.88)	0.17 (0.80)

17. Secondary Outcome

Title	Relative Percent Reduction in Total Thigh Muscle Volume
Description	The effect on relative percent reduction from baseline in total thigh muscle volume measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	3.48 (3.55)	0.68 (3.72)

18. Secondary Outcome

Title	Absolute Reduction in Total Thigh Muscle Volume
Description	The effect on absolute reduction from baseline in total thigh muscle volume measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [Liters]	0.35 (0.35)	0.06 (0.38)

19. Secondary Outcome

Title	Relative Percent Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent
Description	The effect on relative percent reduction from baseline in mean anterior thigh muscle fat infiltration percent measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower risk for metabolic disease.
Time Frame	Baseline,40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	2.81 (6.51)	-0.29 (6.96)

20. Secondary Outcome

Title	Absolute Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent
Description	The effect on absolute reduction from baseline in mean anterior thigh muscle fat infiltration percent measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. Negative values reflect an increase in the value from baseline to study endpoint. Reduction in this variable is believed to be associated with lower risk for metabolic disease
Time Frame	Baseline,40 weeks

Outcome Measure Data

Analysis Population Description

Those who completed baseline and endpoint MRI with interpretable images are reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percentage of fat infiltration]	0.23 (0.49)	0.01 (0.58)

21. Secondary Outcome

Title	Change From Baseline in VAT/SAT Ratio
Description	The effect on absolute reduction from baseline in Visceral adipose tissue/subcutaneous adipose tissue (VAT/SAT) ratio measured by MRI after 40 weeks on treatment versus placebo. Positive numbers reflect the reduction in the value from baseline to study endpoint. This is the ratio of visceral adipose tissue to subcutaneous adipose tissue and it is thought that lower values (relatively less visceral adipose tissue) are better.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [ratio]	0.01 (0.03)	0 (0.02)

22. Secondary Outcome

Title	Change From Baseline in Total Fat/Fat-free Mass Ratio
Description	The effect on absolute change from baseline in total fat/fat-free mass ratio measured by MRI after 40 weeks on treatment versus placebo. This is a ratio of fat to lean mass and it is believed that lower values (less fat relative to lean mass) is better.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [ratio]	-7.23 (7.25)	0.01 (7.83)

23. Secondary Outcome

Title	Relative Percent Change in Fasting Blood Glucose
Description	The relative percent change in fasting blood glucose from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a reduction. This is a blood based biomarker for diabetes in which normal levels are desirable (70-100 mg/dL).
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [percent change]	-5.62 (10.77)	0.83 (13.31)

24. Secondary Outcome

Title	Relative Percent Change in Insulin
Description	The relative percent change in insulin from baseline to study end point as a percent of baseline by treatment group. Positive values reflect an increase. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. This is a blood based biomarker in which lower fasting levels are desirable.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	72	54
Mean (Standard Deviation) [percent change]	20.58 (70.69)	7.73 (58.09)

25. Secondary Outcome

Title	Relative Percent Change in HOMA-IR
Description	The relative percent change in HOMA-IR from baseline to study end point as a percent of baseline by treatment group. Positive values reflect an increase. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. The relative percent change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline to study end point by treatment group measures insulin resistance. Levels above 1.9 signal early insulin resistance, while levels above 2.9 signal significant insulin resistance. There will be optimal insulin sensitivity if HOMA-IR is less than 1.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	72	54
Mean (Standard Deviation) [percent change]	15.35 (71.44)	11.85 (69.0)

26. Secondary Outcome

Title	Relative Percent Change in C-reactive Protein
Description	The relative percent change in biomarker of inflammation: C-reactive protein (CRP) from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. This is a blood based test for which lower values are associated with less inflammation and lower risk for cardiovascular events.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	27	30
Mean (Standard Deviation) [percent change]	-19.91 (32.75)	19.02 (76.13)

27. Secondary Outcome

Title	Relative Percent Change in Triglyceride/HDL-C Ratio
Description	The relative percent change in triglyceride/HDL-C ratio from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. Lower ratio of triglycerides to HDL-cholesterol is associated with less insulin resistance and lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	42	32
Mean (Standard Deviation) [percent change]	-2.10 (30.23)	-2.18 (28.97)

28. Secondary Outcome

Title	Relative Percent Change in Nt-proBNP
Description	The relative percent change in N-terminal Pro Brain Natriuretic Peptides (Nt-proBNP) from baseline to study end point as a percent of baseline by treatment group. Negative values reflect a decrease. Collection was impacted by coronavirus disease 2019 (COVID-19) and limitations to in person study visits, limiting complete collection of data for this measure. NT-proBNP is a blood based biomarker. Lower levels are associated with lower risk for heart failure and cardiovascular events.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	58	40
Mean (Standard Deviation) [percent change]	12.10 (78.5)	20.47 (79.42)

29. Secondary Outcome

Title	Absolute Change in Fasting Blood Glucose
Description	The change in fasting blood glucose from baseline to study end point by treatment group.
Time Frame	Baseline,40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [mg/dL]	-6.49 (12.41)	-0.22 (12.93)

30. Secondary Outcome

Title	Absolute Change in Insulin
Description	The absolute change in insulin from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	72	54
Mean (Standard Deviation) [mIU/L]	0.75 (9.67)	-1.48 (12.26)

31. Secondary Outcome

Title	Absolute Change in HOMA-IR
Description	The absolute change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline to study end point by treatment group measures insulin resistance. Levels above 1.9 signal early insulin resistance, while levels above 2.9 signal significant insulin resistance. There will be optimal insulin sensitivity if HOMA-IR is less than 1. Collection was impacted by COVID-19 and changes to study visits.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	72	54
Mean (Standard Deviation) [Molar units]	-0.15 (3.15)	-0.69 (5.24)

32. Secondary Outcome

Title	Absolute Change in CRP
Description	The change in Markers of inflammation: C-reactive protein (CRP) from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. This is a blood based test for which lower values are associated with less inflammation and lower risk for cardiovascular events.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	27	30
Mean (Standard Deviation) [mg/L]	-2.18 (3.37)	-0.64 (6.23)

33. Secondary Outcome

Title	Absolute Change in Triglyceride/HDL-C Ratio
Description	The change in triglyceride/HDL-C ratio from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. Lower ratio of triglycerides to HDL-cholesterol is associated with less insulin resistance and lower cardiovascular risk.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	42	32
Mean (Standard Deviation) [ratio]	-0.02 (0.83)	-0.16 (0.69)

34. Secondary Outcome

Title	Absolute Change in Nt-proBNP
Description	The change in N-terminal Pro Brain Natriuretic Peptides (Nt-proBNP) from baseline to study end point by treatment group. Collection was impacted by COVID-19 and changes to study visits. NT-proBNP is a blood based biomarker. Lower levels are associated with lower risk for heart failure and cardiovascular events.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

Complete case analysis was done. Those who completed baseline and endpoint study visits and had results, were only analyzed and reported here.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	58	40
Mean (Standard Deviation) [pg/mL]	-8.10 (48.82)	1.44 (41.04)

35. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	The change in heart rate/pulse from baseline to study endpoint visit by treatment group.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [beats per minute]	4.84 (12.95)	2.67 (11.39)

36. Secondary Outcome

Title	Change From Baseline in Blood Pressure
Description	The change in systolic blood pressure from baseline to study endpoint visit by treatment group.
Time Frame	Baseline, 40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [mmHg]	-5.84 (17.98)	-0.02 (16.01)

37. Other Pre-specified Outcome

Title	On-treatment Time, Weeks
Description	The mean duration of treatment during study follow-up.
Time Frame	weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.	Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Measure Participants	73	55
Mean (Standard Deviation) [weeks]	36.2 (8.6)	36.1 (8.2)

Adverse Events

Time Frame	For the entire duration of the study: 40 weeks.
Adverse Event Reporting Description	Adverse events collected at each study visit. GI side effects captured and reported in summary form.
Arm/Group Title	Liraglutide 3.0 mg		Placebo
Arm/Group Description	Drug: Liraglutide Active Drug Other Names: Saxenda Escalate the liraglutide (active) dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Liraglutide: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.		Drug: Placebo (for Liraglutide at a concentration of 6.0 mg/mL) Placebo tablet manufactured to mimic Liraglutide at a concentration of 6.0 mg/mL Other Names: Placebo Saline injection Escalate the Placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day through subcutaneous injection. Placebo: Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
All Cause Mortality
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/93 (0%)
Serious Adverse Events
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/92 (57.6%)		34/93 (36.6%)
Gastrointestinal disorders
GI related	43/92 (46.7%)	43	12/93 (12.9%)	12
Immune system disorders
fever	2/92 (2.2%)	2	0/93 (0%)	0
Infections and infestations
Respiratory Tract infection	10/92 (10.9%)	10	14/93 (15.1%)	14
Musculoskeletal and connective tissue disorders
joint pain	5/92 (5.4%)	5	3/93 (3.2%)	3
Nervous system disorders
headache	5/92 (5.4%)	5	5/93 (5.4%)	5
insomnia	2/92 (2.2%)	2	0/93 (0%)	0
dizziness	3/92 (3.3%)	3	0/93 (0%)	0
Product Issues
Injection site reaction	7/92 (7.6%)	7	8/93 (8.6%)	8

Limitations/Caveats

Results reported according to updated statistical analysis plan published 7/28/2020 on CT.gov website. The updated 7/28/2020 analysis plan accounted for changes in data collection (blood biomarkers) during COVID-19 pandemic and was submitted and published prior to study completion and prior to study un-blinding with updated terminology for study endpoints compared to original protocol.

More Information

Certain Agreements

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

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.