Liraglutide 3mg (Saxenda) on Weight, Body Composition, Ho... | NCT03480022

Status Module

Name	Class
Novo Nordisk A/S	INDUSTRY

Description Module

Detailed Description

The drug, liraglutide 3.0 mg was approved for chronic weight management in management in obese adults with an initial BMI of 30 kg/m2 or greater or in overweight adults BMI of 27 kg/m2 or greater with at least one weight-related co-morbid condition as an adjunct to a reduced-calorie diet and increased physical activity. Liraglutide is an acylated human glucagon-like peptide -1 (GLP-1) analog that binds to and activates the GLP-1 receptor. It lowers body weight through decreased caloric intake while stimulating insulin secretion and reducing glucagon via a glucose-dependent mechanism. For obesity management, patients may lose weight with GLP-1 receptor agonists due to other unique actions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can slow gastric emptying and increase satiety. While predictors of weight loss success for the general population are available (protein intake, weight loss medications), predictors of weight loss success may differ between normal and hyperandrogenic women. Glucagon-like peptide 1 agonists are linked with dose dependent weight lowering potential in different obesity related populations. The weight loss effects of GLP-1RAs previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to patients with PCOS.

Given this lack of information, the aim of the present study was to investigate the effects of liraglutide 3mg vs. placebo on body composition as well as hormonal and metabolic features in non-diabetic obese women with PCOS.The non-diabetic obese female with PCOS offers a unique model to study the relationship between insulin resistance and adiposity. The investigators propose a double-blind, placebo-controlled 30-week trial designed to directly examine the therapeutic effects of liraglutide 3 mg (LIRA 3 mg) compared to placebo on body weight, hormonal and cardiometabolic parameters in obese non-diabetic women with PCOS. All patients will receive diet and lifestyle counseling, including advice on exercise commencing during the lead-in period and continuing throughout the study. In this study, the investigators will examine the efficacy of LIRA 3mg on body weight and body composition, reproductive function metabolic parameters and cardiovascular risk factors in a well-defined group of pre-menopausal obese non-diabetic women with hyperandrogenism, focusing on the relationship to obesity and insulin resistance.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liraglutide Pen Injector (Saxenda)	Experimental	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily	Drug: Liraglutide Pen Injector [Saxenda]
Placebo liraglutide pen injector	Placebo Comparator	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily	Drug: Placebo Liraglutide Pen Injector

Name	Type	Description	Arm Group Labels	Other Names
Liraglutide Pen Injector [Saxenda]	Drug	daily sc injection of liraglutide with final dose of 3mg daily	Liraglutide Pen Injector (Saxenda)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Body Weight (BW)	Treatment impact on change in body weight after 32 weeks of treatment.	32 weeks of treatment
Free Androgen Index (FAI)	Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic).	32 weeks of treatment

Secondary Outcomes

Measure	Description	Time Frame
Body Mass Index (BMI)	Treatment effect in reducing body mass	32 weeks of treatment
Change in Percent Body Weight	Treatment effect on reducing body weight expressed as percent body weight loss from baseline

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Female gender
18-45 years of age
BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with one or more obesity-associated co-morbid conditions (e.g. hypertension, and dyslipidemia)
PCOS- NIH criteria hyperandrogenism and irregular menstrual cyclicity
Non-diabetic as determined by a 75 gram oral glucose tolerance test (OGTT) and hemoglobin A1C. Non-diabetic is inclusive of women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT). Participants with diabetes will be excluded
Willing to use effective contraception consistently during therapy which is defined as:
- an intrauterine device, tubal sterilization, or male partner vasectomy, or
- combination of two barrier methods with one being male condom.
Written consent for participation in the study

Exclusion Criteria:

Presence of significant systemic disease, cerebrovascular disease, clinically significant cardiac abnormalities or heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or clinically significant elevations in prolactin levels. The clinical significance of prolactin levels will be determined by the treating physician
Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)
Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
Use of hormonal medications, the use of medications that cause clinically significant weight gain or loss (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, GnRH analogues, glucocorticoids, anabolic steroids, C-19 progestins) including herbal medicines for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) for at least 4 weeks
Prior history of a malignant disease requiring chemotherapy
Family or personal history of familial medullary thyroid carcinoma or multiple endocrine neoplasia type 2
Known hypersensitivity or contraindications to use GLP1 receptor agonists
Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium/glucose co-transporter 2 (SGLT2) inhibitors or weight loss medications (prescription or OTC) stopped for at least 4 weeks
Prior use of medication to treat diabetes except gestational diabetes
Eating disorders (anorexia, bulimia) or gastrointestinal disorders
Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in next 15 months, breastfeeding, or known pregnancy in last three months
Active or prior history of substance abuse (smoke or tobacco use within past 6 months) or significant intake of alcohol
Previous bariatric surgery or device intervention for obesity
Patient not willing to use barrier contraception during study period (unless sterilized or have an IUD)
History of major depressive or other severe psychiatric disorders
Inability or refusal to comply with protocol
Currently participating or having participated in an experimental drug study in previous three months

Name	Affiliation	Role
Peggy Dean, PharmD	Woman's Hospital Foundation IRB	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Woman's Hospital		Baton Rouge	Louisiana	70817	United States

PubMed Identifier	Type	Citation	Retractions
35710599	Derived	Elkind-Hirsch KE, Chappell N, Shaler D, Storment J, Bellanger D. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study. Fertil Steril. 2022 Aug;118(2):371-381. doi: 10.1016/j.fertnstert.2022.04.027. Epub 2022 Jun 13.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 15, 2018

Arm/Group Information

ID	Title	Description
BG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
BG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00055 BG00127 BG00282

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Absolute Body Weight (BW)

Treatment impact on change in body weight after 32 weeks of treatment.

Posted

Mean

Standard Error

kilogram

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG00044 OG00123

Title

Denominators

Categories

Title	Measurements
	OG000104.7± 2.9 OG001117.9± 5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effect	ANOVA	Nested repeated measures design	<0.002														Superiority

Primary

Free Androgen Index (FAI)

Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic).

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Body Mass Index (BMI)

Treatment effect in reducing body mass

Posted

Mean

Standard Error

kilogram/meter squared

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Change in Percent Body Weight

Treatment effect on reducing body weight expressed as percent body weight loss from baseline

Posted

Mean

Standard Error

percentage loss in body weight

Change from baseline (time 0) to study end (32 weeks)

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

5% Weight Loss From Baseline

Frequency of patients achieving 5% weight loss from baseline with treatment

Posted

Count of Participants

Participants

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

10% Body Weight Loss From Baseline

Frequency of patients with at least 10% reduction in body weight from baseline

Posted

Count of Participants

Participants

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Abdominal Adiposity (Waist Circumference [WC]

Treatment effect on loss of WC (abdominal adiposity) with drug treatment

Posted

Mean

Standard Error

centimeters

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Waist-to-Hip Ratio

Change in central adiposity with treatment as measured by WHR. A reduction in ratio indicates a decrease in truncal fat.

Posted

Mean

Standard Error

ratio

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Waist-to Height Ratio [WHtR])

Treatment effect on loss of central adiposity as determined by WHt ratio. The lower the ratio indicates less abdominal adiposity.

Posted

Mean

Standard Error

ratio

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Total Fat Mass Evaluated by DEXA

Treatment effect on reduction of fat mass (kg)

Posted

Mean

Standard Error

kilogram

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Total Body Fat (%) by DXA

Treatment effect on reduction of percent body fat by DXA

Posted

Mean

Standard Error

percent fat mass

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Android-Gynoid Ratio (AGR) by DXA

Treatment impact on AGR, measure of central adiposity, as determined by DXA. A lower AGR indicates a reduction in central adiposity.

Posted

Mean

Standard Error

ratio

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Trunk/Leg Fat Ratio (TLR) by DXA

Treatment impact on TLR after 32 weeks. A reduction in TLR indicates a loss of central fat.

Posted

Mean

Standard Error

ratio

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Menstrual Cycle Frequency

Drug treatment impact on normalization of cycle frequency (cycle every 28-30 days). All cycle data is expressed as number of menses annualized to one year.

Posted

Mean

Standard Error

menses per year

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Total Testosterone Concentrations (T)

Drug treatment effect on total testosterone concentrations

Posted

Mean

Standard Error

ng/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Adrenal Dehydroepiandrosterone Sulfate (DHEAS)

Treatment efficacy in reducing adrenal hyperandrogenism

Posted

Mean

Standard Error

mcg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Fasting Blood Glucose (FG)

Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)

Posted

Mean

Standard Error

mg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

OGTT Mean Blood Glucose (MBG)

Treatment effect on MBG measured during the oral glucose tolerance test. A decrease in MBG shows improvement in glycemia.

Posted

Mean

Standard Error

mg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Fasting Insulin Sensitivity (HOMA-IR)

Treatment effect on the HOMA-IR which is an insulin resistance measured derived from fasting blood glucose and insulin . The higher the number the more insulin resistant.

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)

The SI OGTT is a measure of peripheral insulin sensitivity derived from the insulin and glucoses measured during an OGTT. A increase in SI OGTTindicates greater insulin sensitivity

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Corrected First Phase Insulin Secretion (IGI/HOMA-IR)

Treatment effect on insulin secretion from 0 to 30 minutes after glucose load corrected for by fasting insulin sensitivity. A higher score shows improved first phase insulin secretion in response to glucose.

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI)

Treatment effect on an estimation of Beta cell compensatory function, the IS-SI is derived by applying the concept of the disposition index to measurements obtained during the 2 hour OGTT and calculated as the index of insulin secretion factored by insulin sensitivity. A higher score shows improved pancreatic beta cell function relative to insulin sensitivity.

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units

Secondary

Total Cholesterol Levels

Treatment impact on improving total cholesterol levels

Posted

Mean

Standard Error

mg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

High Density Lipoprotein Cholesterol (HDL-C)

Impact of treatment on HDL levels after 32 weeks of treatment

Posted

Mean

Standard Error

mg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Triglyceride Levels (TRG)

Drug effect of TRG levels after treatment

Posted

Mean

Standard Error

mg/dL

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C)

Treatment impact on TRG/HDL-C ratio which is a simple measure to estimate insulin action. A decrease in ratio indicates improvement in insulin sensitivity.

Posted

Mean

Standard Error

ratio

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Triglyceride and Glucose Index (TyG)

Treatment impact on the TyG index which estimates insulin resistance. A reduction in TyG indicates an improvement in insulin action.

Posted

Mean

Standard Error

index score

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants

Secondary

Systolic Blood Pressure

Treatment impact on systolic blood pressure

Posted

Mean

Standard Error

mmHg

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Secondary

Diastolic Blood Pressure (BP)

Treatment impact on reducing diastolic blood pressure

Posted

Mean

Standard Error

mmHg

32 weeks of treatment

ID	Title	Description
OG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily
OG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Liraglutide Pen Injector (Saxenda)	Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily Liraglutide Pen Injector [Saxenda]: daily sc injection of liraglutide with final dose of 3mg daily	0	55	0	55	40	55
EG001	Placebo Liraglutide Pen Injector	Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo	0	27	0	27	8	27

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG00014 affected55 at risk EG0013 affected27 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	EG0002 affected55 at risk EG0010 affected27 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0005 affected55 at risk EG0010 affected27 at risk
Diarrhea	Gastrointestinal disorders	Non-systematic Assessment	EG0004 affected55 at risk EG0010 affected27 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0003 affected55 at risk EG0011 affected27 at risk
Heartburn	Gastrointestinal disorders	Non-systematic Assessment	EG0002 affected55 at risk EG0011 affected27 at risk
Reflux	Gastrointestinal disorders	Non-systematic Assessment	EG0002 affected55 at risk EG0010 affected27 at risk
Indigestion	Gastrointestinal disorders	Non-systematic Assessment	EG0002 affected55 at risk EG0010 affected27 at risk
Injection site reaction	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0003 affected55 at risk EG0010 affected27 at risk
prolonged menstrual bleeding	Reproductive system and breast disorders	Non-systematic Assessment	EG0003 affected55 at risk EG0011 affected27 at risk
no menses	Reproductive system and breast disorders	Non-systematic Assessment	EG0000 affected55 at risk EG0011 affected27 at risk
COVID-19	Infections and infestations	Non-systematic Assessment	EG0000 affected55 at risk EG0011 affected27 at risk

ID	Term
D018149	Glucose Intolerance
D011085	Polycystic Ovary Syndrome
D056128	Obesity, Abdominal
D011236	Prediabetic State
D015431	Weight Loss

ID	Term
D006943	Hyperglycemia
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D010048	Ovarian Cysts
D003560	Cysts
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D006058	Gonadal Disorders
D004700	Endocrine System Diseases
D009765	Obesity
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D003920	Diabetes Mellitus
D001836	Body Weight Changes

ID	Term
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists