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Completed

NCT Number: NCT05548647

Semaglutide Treatment, Appetite, and Eating Behavior: Long-term Effects

This study will evaluate the effect of semaglutide on eating behavior, appetite (hunger/fullness), and food liking in the long-term, as compared to placebo. All participants will receive lifestyle modification (diet and exercise) counseling, and will be prescribed the FDA-approved weight loss medication, semaglutide, or placebo (an inactive saline solution) for 72 weeks.

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Key information

Conditions

Obesity Appetitive Behavior Behavior Behavior, Animal Body Weight Body Weight Changes Motor Activity Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Pennsylvania Center for Weight and Eating Disorders

Philadelphia, Pennsylvania, 19104, United States

About this study

This trial consists of a single 72-week treatment period during which two studies will be conducted. Study 1 (i.e., long-term treatment trial; weeks 0-60) is a 60-week, single center, double-blinded, randomized controlled, parallel group design trial, and Study 2 (i.e., re-randomized medication withdrawal trial; weeks 60-72) is a separate, 12-week, double-blind, re-randomized medication withdrawal trial.

The long-term treatment trial (Study 1) will randomly assign (in a 3:2 semaglutide:placebo ratio) 120 subjects with a body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related co-morbidities, to 60 weeks of: 1) placebo with moderate intensity lifestyle intervention (as used in STEP 1); or 2) semaglutide 2.4 mg with the same lifestyle intervention. All subjects will receive 60 weeks of trial product, which will be up-titrated over 16 weeks in those assigned to semaglutide 2.4 mg. They will complete assessments of energy intake, appetite, food reward, mood, symptoms of disordered eating, and anthropomorphic measurements at baseline (week 0) and weeks 20, 40, and 60.

The primary aim in the initial long-term treatment trial will be to compare the long-term effect of semaglutide 2.4 mg vs placebo on ad libitum energy intake during a lunch meal at weeks 20, 40, and 60. Confirmatory secondary aims will test the effect of semaglutide 2.4 mg at weeks 20, 40 and 60 on subjective appetite ratings (both measured during a standardized breakfast in the lab and as experienced more globally over the past week), explicit food reward, as measured with the Power of Food Scale (24), and implicit food reward, as measured with the Leeds Food Preference Task (25, 26). Measures of food cravings, mood, eating disorder symptoms, and self-report measures of eating behavior will be considered supportive secondary endpoints and will provide additional evidence of the medication's safety and efficacy.

Following the completion of Study 1 at week 60, all subjects who complete a week 60 assessment and remain on drug will be enrolled in Study 2. Semaglutide-treated subjects will be re-randomized (in a 1:4 semaglutide:placebo ratio) to receive semaglutide 2.4 mg or placebo for 12 weeks. All subjects originally assigned to placebo will continue with that medication for an additional 12 weeks. Both researchers and subjects will remain blinded to subjects' original and re-randomized (or continued) treatment assignments. The goal of this re-randomized medication withdrawal period will be to compare the 80% of subjects originally assigned to semaglutide 2.4 mg who receive placebo at week 60 (semaglutide-to-placebo group) to the subjects originally randomized to placebo (continuous-placebo group) on all primary and secondary outcome measures at week 72 (after controlling for Study 1 baseline/week 0 values). All subjects will terminate trial product at cumulative week 72 and will return to clinic for a final safety visit at week 76.

Outcome assessments including ad libitum energy intake, subjective measures of appetite, food reward, eating behavior, mood, and eating disorder symptoms will occur at weeks 0, 20, 40, and 60 of Study 1 and at week 12 (72 weeks from original randomization) of the re-randomized treatment period. Measurements of body weight, waist circumference, blood pressure, pulse, and global, past-week appetite and food cravings (COEQ) also will be collected every 4 weeks throughout both treatment studies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men and women who report a desire to lose weight
  • Aged 18-70 years
  • Body mass index [BMI] ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with an obesity-related comorbidity (e.g., treated or untreated hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease)
  • Eligible female patients will be:
  • non-pregnant, evidenced by a negative urine pregnancy test
  • non-lactating
  • surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study
  • Subjects must
  • Plan to remain in the Philadelphia area for the next 1.5 years.
  • Ability to provide informed consent before any trial-related activities.

Exclusion criteria

  • A diagnosis of type I or II diabetes
  • Hemoglobin A1c (HbA1c) > 6.5%
  • Uncontrolled hypertension (blood pressure ≥ 160/100 mm Hg)
  • Clinically significant hepatic (i.e., liver fibrosis, cirrhosis or confirmed NASH) or renal disease
  • Uncontrolled thyroid disease
  • Experienced a cardiovascular event (e.g., stroke, myocardial infarction) in the last 6 months, congestive heart failure, or heart block greater than first degree
  • A history of acute pancreatitis in the last 6 months
  • Any history of chronic pancreatitis
  • A history of malignancy (other than non-melanoma skin cancer) within the last 5 years
  • A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
  • A self-reported change in body weight >5kg (11 lbs) within 90 days before screening
  • Used within the last 6 months medications known to produce weight loss/gain (e.g., medications approved for weight loss, oral steroids, antipsychotic medications) or any GLP-1 receptor agonist.
  • Known or suspected allergy or hypersensitivity to trial medication(s), excipients, or related products
  • The receipt of any investigational drug within 6 months prior to this trial
  • Applicants with current severe major depressive disorder (BDI-II score ≥ 29 or Patient Health Questionnaire-9 [PHQ-9] score > 15) or severe anxiety disorder
  • Applicants with current, active suicidal ideation, and/or a suicide attempt within the past year (such individuals will be referred for psychiatric treatment if they have not previously received it).
  • Any severity of psychotic or bipolar disorder
  • Bulimia nervosa diagnosis within the past 5 years
  • Self-reported alcohol or substance abuse within the past 6 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
  • History of (or plans to receive in the next 1.5 years) bariatric surgery or a weight loss device. (However, the following will be allowed: liposuction or abdominoplasty > 1 year before screening, laparoscopic banding if removed > 1 year before screening, intragastric balloon or aspire assist if removed > 1 year before screening.)
  • Inability to walk 5 blocks or more (comfortably) or engage in another form of aerobic activity.
  • Women who are nursing, pregnant, or planning to become pregnant in the next 1.5 years or are not using adequate contraceptive measures
  • Previous participation in this trial (e.g., randomized but failed to participate)
  • Changes to any chronic medication (type or dosage) within the past 3 months.
  • Food allergy or dietary preference that would prevent the individual from consuming the standard breakfast or ad libitum lunch.
  • To be eligible to participate in the re-randomized treatment period from weeks 60 to 72, subjects must also:
  • complete a week 60 assessment
  • be classified as "on drug" as at the week 60 assessment and report taking at least one dose of trial product within the past 2 weeks

Treatment and study plan

Behavioral Treatment

Behavioral

All participants, regardless of medication assignment, will receive the same 60-week behavioral weight loss program. Brief (15-minute), individual lifestyle counseling sessions will be delivered by a psychologist, behavioral health counselor, or registered dietitian (or other trained health care provider) at weeks 0 (i.e., baseline/randomization), 2, 4 and every fourth week from week 4 to week 60 (17 sessions) of Study 1. Subjects will be instructed to consume a self-selected diet of 1200-1500 kcal/day (for those who weigh < 250 lb) or 1500-1800 kcal/day (for those who weigh ≥250 lb). They will be instructed to engage in low-to-moderate intensity physical activity (e.g., walking), gradually building to a goal of ≥150 minutes per week (spread across 5 days) by week 40. They will be instructed to use calorie counting and self-monitoring to meet their goals.

Other names: Lifestyle modification, Behavioral weight loss, Lifestyle intervention

Placebo

Drug

An inactive saline solution administered via subcutaneous injection

Other names: Placebo for medication

Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]

Drug

Semaglutide 2.4 mg is a once weekly subcutaneous glucagon-like peptide-1 (GLP-1) receptor agonist that has been FDA approved for weight loss

Other names: Wegovy

Primary outcomes

  1. Study 1 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Primary outcome (Study 1)

  2. Study 2 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)

    Time frame: S2: Endpoint comparison at week 72

    Primary outcome (Study 2)

Secondary outcomes

  1. Study 1 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): This is a single value calculated by averaging 100-mm VAS ratings for hunger (reversed), fullness, satiety, and prospective food consumption (reversed) as measured when fasting prior to eating a standardized breakfast. Score range 0-100 mm. Higher values indicate greater suppression (i.e., less appetite).

  2. Study 1 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) After Eating (Area Under the Curve)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): This is a single value calculated by averaging 100-mm VAS ratings for hunger (reversed), fullness, satiety, and prospective food consumption (reversed) as measured every 30 minutes in the 4 hours after eating a standardized breakfast. Post-prandial scores were combined into a single area under the curve value using the trapezoidal method. Possible area range: 0 - 24,000. Higher values indicate greater suppression (i.e., less appetite).

  3. Study 1 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): Visual analogue scale rating of hunger during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater hunger.

  4. Study 1 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): Visual analogue scale rating of fullness after meals during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater fullness after meals.

  5. Study 1 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): Visual analogue scale rating of food preoccupation during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater food preoccupation.

  6. Study 1 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): Explicit responsiveness to the food environment measured by the summary score of the Power of Food Scale (15-item version). Score range 1-5. Higher scores indicate greater responsiveness to the food environment.

  7. Study 1 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Secondary confirmatory outcome (Study 1): Implicit food wanting of high-fat, savory foods measured using the Leeds Food Preference Task. Scores range from -100 to +100 with higher scores indicating a greater implicit wanting of high-fat savory foods.

  8. Study 2 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): This is a single value calculated by averaging 100-mm VAS ratings for hunger (reversed), fullness, satiety, and prospective food consumption (reversed) as measured when fasting prior to eating a standardized breakfast. Score range 0-100 mm. Higher values indicate greater suppression (i.e., less appetite).

  9. Study 2 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) After Eating (Area Under the Curve)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): This is a single value calculated by averaging 100-mm VAS ratings for hunger (reversed), fullness, satiety, and prospective food consumption (reversed) as measured every 30 minutes in the 4 hours after eating a standardized breakfast. Post-prandial scores were combined into a single area under the curve value using the trapezoidal method. Possible area range: 0 - 24,000. Higher values indicate greater suppression (i.e., less appetite).

  10. Study 2 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): Visual analogue scale rating of hunger during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater hunger.

  11. Study 2 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): Visual analogue scale rating of fullness after meals during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater fullness after meals.

  12. Study 2 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): Visual analogue scale rating of food preoccupation during the past week (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater food preoccupation.

  13. Study 2 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): Explicit responsiveness to the food environment measured by the summary score of the Power of Food Scale (15-item version). Score range 1-5. Higher scores indicate greater responsiveness to the food environment.

  14. Study 2 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Secondary confirmatory outcome (Study 2): Implicit food wanting of high-fat, savory foods measured using the Leeds Food Preference Task. Scores range from -100 to +100 with higher scores indicating a greater implicit wanting of high-fat savory foods.

Other outcomes

  1. Study 1 Body Weight (kg)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Body weight change (kg)

  2. Study 1 Craving Control Over the Past Week as Measured by the COEQ

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Composite (mean) of visual analogue scale ratings for craving control (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate greater ability to control food cravings.

  3. Study 1 Craving for Savory Over the Past Week as Measured by the COEQ

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Composite (mean) of visual analogue scale ratings for craving for savory foods (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate stronger/more frequent cravings for savory foods.

  4. Study 1 Craving for Sweet Over the Past Week as Measured by the COEQ

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Composite (mean) of visual analogue scale ratings for craving for sweet foods (Control of Eating Questionnaire; COEQ). Score range 0-100 mm. Higher scores indicate stronger/more frequent cravings for sweet foods.

  5. Study 1 Food Cravings as Measured by the General Food Cravings Questionnaire - Trait

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Food cravings as measured by the General Food Cravings Questionnaire - Trait (G-FCQ-T 21-item). Score range 21-126, higher scores indicate more/stronger food cravings.

  6. Study 1 Explicit Liking of High-fat Savory Foods (LFPT)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1) Explicit liking of high-fat savory foods as measured on 100-mm VAS scales (mean of high-fat savory items) during the Leeds Food Preference Task. Score range 0 - 100 mm with higher scores indicating greater liking of high-fat savory foods.

  7. Study 1 Cognitive Restraint (Eating Inventory)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Eating behavior - cognitive restraint subscale of the Eating Inventory (EI). Score range 0-21, higher=more dietary restraint.

  8. Study 1 Disinhibition (Eating Inventory)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Eating behavior - disinhibition subscale of the Eating Inventory. Score range 0-16, higher=more disinhibition.

  9. Study 1 Weight-related Self-efficacy

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1) Mean score on the Weight-related self-efficacy (WEL-short form). Sum of 8 items, score range 0-80, higher scores indicate greater weight-related self-efficacy.

  10. Study 1 Mood as Assessed Using the PHQ-9

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Depressed mood as assessed using the PHQ-9. Score range 0 - 27; higher scores indicate more symptoms of depressed mood.

  11. Study 1 Clinician-rated Binge Eating Frequency (Sum of Objective and Subjective Binge Eating Frequency)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Clinician-rated binge eating frequency (sum of objective and subjective binge eating frequency) in the past 12 weeks as assessed by the Eating Disorder Examination (EDE). Score is the count of binge episodes, range ≥0, more episodes indicates more frequent binge eating in the past 12 weeks.

  12. Study 1 Self-reported Loss-of-control Eating (Loss of Control Eating Scale)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Self-reported loss-of-control eating as measured by the Loss of Control Eating Scale (LOCES). Mean score range 1-5; higher scores indicate greater/more frequent loss of control over eating.

  13. Study 1 Food Addiction Symptoms Measured by Yale Food Addiction Scale

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Exploratory outcome (Study 1): Food addiction symptoms measured by Yale Food Addiction Scale (YFAS). Symptom number range 0-11, higher scores indicate more food addiction symptoms

  14. Study 1 Drive for Thinness (Eating Disorder Inventory [EDI])

    Time frame: Change from baseline to weeks 20, 40, and 60

    Supportive secondary outcome (Study 1): Study 1 Drive for thinness as measured by the Eating Disorder Inventory (EDI). Score range 0-28; higher scores indicate greater drive for thinness.

  15. Study 1 Ratings of Nausea When Fasting

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Exploratory outcome (Study 1): Ratings of nausea using 100 mm visual analogue scales when fasting in the laboratory prior to consuming the standard breakfast meal. Score range 0-100 mm; higher scores indicate greater nausea.

  16. Study 1 Ratings of Food Palatability

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Exploratory outcome (Study 1): Ratings of food palatability using 100 mm visual analogue scales during a laboratory test meal. Score range 0-100 mm; higher scores indicate higher liking of the food taste.

  17. Study 1 Body Image Dissatisfaction (Body Satisfaction Scale)

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Exploratory outcome (Study 1): Body image dissatisfaction (Body Satisfaction Scale). Mean of 13 items, score range 1-7, higher scores indicate greater body part dissatisfaction.

  18. Study 1 Weight-related Self Stigmatization

    Time frame: S1: Change from baseline to weeks 20, 40, and 60

    Exploratory outcome (Study 1): Weight-related self stigmatization by the Weight Bias Internalization Scale. Mean of 11 items; score range 1-7; higher scores indicate greater weight-related self-stigmatization.

  19. Study 2 Body Weight (kg)

    Time frame: S2: Week 72 endpoint controlling for S1 baseline

    Supportive secondary outcome (Study 2): Body weight (kg) at week 72

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • Novo Nordisk A/S

Registry information

Official study title

Short- and Long-term Effects of Once Weekly Semaglutide 2.4 mg on Appetite, Eating Behavior, and Psychosocial Status

Acronym: STABLE Wt Loss

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Sep 21, 2022
Registry last updated
Aug 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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