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

NCT05548647 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 850370
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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, or placebo (an inactive saline solution) for 72 weeks.

Conditions

Obesity

Keywords

Semaglutide; Body weight; Obesity; weight loss; medication; overweight; lifestyle modification; diet; exercise; Body Weight Changes; Appetitive Behavior

Outcome Measures

Primary Outcomes (1)

• Ad libitum energy intake (kcal) during a buffet lunch meal (4 hrs after standardized breakfast)

  Primary outcome

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

Secondary Outcomes (4)

• Laboratory-based appetite measured as a composite of visual analogue scale ratings (hunger, fullness, satiety, prospective consumption) when fasting and after eating (area under the curve). This is a single outcome calculated by combining the VAS ratings

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

• Global subjective appetite (e.g., hunger, fullness, food preoccupation) over the past week measured using the Control of Eating Questionnaire (COEQ)

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

• Explicit responsiveness to the food environment measured by the summary score of the Power of Food Scale (15-item version)

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

• Implicit food wanting of high-fat, savory foods measured using the Leeds Food Preference Task

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

Other Outcomes (14)

• Food cravings over the past week as measured by the COEQ (Three factors: craving control, craving for sweet foods, craving for savory foods)

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

• Food cravings as measured by the General Food Cravings Questionnaire - Trait

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

• Explicit food liking measured during the Leeds Food Preference Task

  S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline

Study Arms (2)

Behavioral Treatment + Placebo

ACTIVE COMPARATOR

Behavioral treatment (lifestyle modification counseling for weight loss) plus placebo

Behavioral: Behavioral Treatment; Drug: Placebo

Behavioral Treatment + Medication

ACTIVE COMPARATOR

Behavioral treatment (lifestyle modification counseling for weight loss) plus semaglutide

Behavioral: Behavioral Treatment; Drug: Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]

Interventions

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.

Also known as: Lifestyle modification, Behavioral weight loss, Lifestyle intervention

Behavioral Treatment + Medication; Behavioral Treatment + Placebo

Placebo DRUG

An inactive saline solution administered via subcutaneous injection

Also known as: Placebo for medication

Behavioral Treatment + Placebo

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

Also known as: Wegovy

Behavioral Treatment + Medication

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

University of Pennsylvania Center for Weight and Eating Disorders

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Gordon 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.

  PMID: 38655793 DERIVED

MeSH Terms

Conditions

Obesity; Body Weight; Weight Loss; Overweight; Motor Activity; Body Weight Changes; Appetitive Behavior

Interventions

Behavior Therapy; Dosage Forms; semaglutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Behavior, Animal

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 21, 2022
• Study Start: July 26, 2022
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

US (1)