ObesityPhase 4STABLE Wt LossNCT05548647
Semaglutide Treatment, Appetite, and Eating Behavior: Long-term Effects
A Phase 4 study testing Behavioral Treatment and Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY] in people with Obesity, run by University of Pennsylvania at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Obesity
- What is being tested?
- Behavioral Treatment and Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2022to 12 May 2025
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
- 1. 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Center for Weight and Eating Disorders
Philadelphia, Pennsylvania, 19104
About this study
Official title: Short- and Long-term Effects of Once Weekly Semaglutide 2.4 mg on Appetite, Eating Behavior, and Psychosocial Status
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.
Read the detailed description
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.
- Conditions
- Obesity
- Being tested
- Behavioral Treatment, Placebo, Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]
- Keywords
- Semaglutide, Body weight, Obesity, weight loss, medication, overweight, lifestyle modification, diet, exercise, Body Weight Changes, Appetitive Behavior
- Medical subject headings
- Obesity, Body Weight, Weight Loss, Overweight, Motor Activity, Body Weight Changes, Appetitive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Behavioral TreatmentBehavioural
Also called Lifestyle modification, Behavioral weight loss, Lifestyle intervention
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.
PlaceboDrug
Also called Placebo for medication
An inactive saline solution administered via subcutaneous injection
Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]Drug
Also called Wegovy
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
| Study group | Role | What they receive |
|---|---|---|
| Behavioral Treatment + Placebo (weeks 0-60) // Continuous Placebo (weeks 60-72) | Active comparator | Behavioral treatment (lifestyle modification counseling for weight loss) plus placebo from weeks 0 - 60.
At week 60, all placebo-treated participants were (sham) re-randomized to continue placebo for an additional 12 weeks (i.e., continuous placebo group). Receives: Behavioral: Behavioral Treatment; Drug: Placebo |
| Behavioral Treatment + Medication (weeks 0-60) // Switched to Placebo (weeks 60-72) | Active comparator | Behavioral treatment (lifestyle modification counseling for weight loss) plus semaglutide from weeks 0 to week 60.
At week 60, semaglutide-treated participants were re-randomized 4:1 to either switch to placebo or continue semaglutide for an additional 12 weeks (weeks 60 - 72). By re-allocating a small number of subjects to semaglutide-to-semaglutide at week 60, both researchers and subjects remain blinded to medication condition during the re-randomized treatment period. However, the semaglutide-to-semaglutide group was not intended to be subject to statistical analysis. Therefore the week 72 results for this group represent those of the semaglutide-to-placebo group who took semaglutide for 60 weeks and then placebo for the last 12 weeks. Receives: Behavioral: Behavioral Treatment; Drug: Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study 1 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)
Primary outcome (Study 1)
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 2 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)
Primary outcome (Study 2)
Measured: S2: Endpoint comparison at week 72
Secondary outcomes (14)
Study 1 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting
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).
Measured: S1: Change from baseline to weeks 20, 40, and 60
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)
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).
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 1 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 1 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 1 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 1 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)
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.
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 1 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task
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.
Measured: S1: Change from baseline to weeks 20, 40, and 60
Study 2 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting
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).
Measured: S2: Week 72 endpoint controlling for S1 baseline
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)
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).
Measured: S2: Week 72 endpoint controlling for S1 baseline
Study 2 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S2: Week 72 endpoint controlling for S1 baseline
Study 2 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S2: Week 72 endpoint controlling for S1 baseline
Study 2 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)
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.
Measured: S2: Week 72 endpoint controlling for S1 baseline
Study 2 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)
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.
Measured: S2: Week 72 endpoint controlling for S1 baseline
Study 2 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task
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.
Measured: S2: Week 72 endpoint controlling for S1 baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start26 Jul 2022
- Primary completion12 May 2025
- Study completion12 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study 1 is a double-blind, placebo-controlled, randomized controlled, long-term treatment trial. Study 2 is a double-blind, medication withdrawal trial, re-randomized treatment trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05548647
- Sponsor's protocol ID
- 850370
- Acronym
- STABLE Wt Loss
- Status last verified
- Jul 2026
- First submitted
- 14 Sep 2022
- Last updated
- 3 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tronieri JS, Allison KC, DeRouen K, Amaro A, Collins KG, Roy A, Watts S, Ananna T, Wadden TA. Short- and long-term effects of semaglutide 2.4 mg on energy intake, appetite, and food reward: a 60-week, double-blind randomized controlled trial. Am J Clin Nutr. 2026 Aug;124(2):101403. doi: 10.1016/j.ajcnut.2026.101403. Epub 2026 Jun 20.
PubMed 42323166Gordon K, Matthews A, Zeller MH, Lin J. Practical guidelines for eating disorder risk mitigation in patients undergoing obesity treatment for the pediatric provider. Curr Opin Pediatr. 2024 Aug 1;36(4):367-374. doi: 10.1097/MOP.0000000000001356. Epub 2024 Apr 5.
PubMed 38655793