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

NCT ID: NCT05548647

Last Updated: 2025-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-26
• Study Completion Date: 2025-05-12

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Behavioral Treatment + Placebo

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

Group Type: ACTIVE_COMPARATOR

Behavioral Treatment

Intervention Type: 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.

Placebo

Intervention Type: DRUG

An inactive saline solution administered via subcutaneous injection

Behavioral Treatment + Medication

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

Group Type: ACTIVE_COMPARATOR

Behavioral Treatment

Intervention Type: 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.

Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]

Intervention Type: 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

Interventions

Behavioral Treatment

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.

Intervention Type: BEHAVIORAL

Placebo

An inactive saline solution administered via subcutaneous injection

Intervention Type: DRUG

Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [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

Intervention Type: DRUG

Other Intervention Names

Lifestyle modification; Behavioral weight loss; Lifestyle intervention; Placebo for medication; Wegovy

Eligibility Criteria

Inclusion Criteria

1. Men and women who report a desire to lose weight

2. Aged 18-70 years

3. 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)

4. 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

5. 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

1. A diagnosis of type I or II diabetes

2. Hemoglobin A1c (HbA1c) > 6.5%

3. Uncontrolled hypertension (blood pressure ≥ 160/100 mm Hg)

4. Clinically significant hepatic (i.e., liver fibrosis, cirrhosis or confirmed NASH) or renal disease

5. Uncontrolled thyroid disease

6. Experienced a cardiovascular event (e.g., stroke, myocardial infarction) in the last 6 months, congestive heart failure, or heart block greater than first degree

7. A history of acute pancreatitis in the last 6 months

8. Any history of chronic pancreatitis

9. A history of malignancy (other than non-melanoma skin cancer) within the last 5 years

10. A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2

11. A self-reported change in body weight >5kg (11 lbs) within 90 days before screening

12. 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.

13. Known or suspected allergy or hypersensitivity to trial medication(s), excipients, or related products

14. The receipt of any investigational drug within 6 months prior to this trial

15. Applicants with current severe major depressive disorder (BDI-II score ≥ 29 or Patient Health Questionnaire-9 [PHQ-9] score > 15) or severe anxiety disorder

16. 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).

17. Any severity of psychotic or bipolar disorder

18. Bulimia nervosa diagnosis within the past 5 years

19. Self-reported alcohol or substance abuse within the past 6 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)

20. 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.)

21. Inability to walk 5 blocks or more (comfortably) or engage in another form of aerobic activity.

22. Women who are nursing, pregnant, or planning to become pregnant in the next 1.5 years or are not using adequate contraceptive measures

23. Previous participation in this trial (e.g., randomized but failed to participate)

24. Changes to any chronic medication (type or dosage) within the past 3 months.

25. Food allergy or dietary preference that would prevent the individual from consuming the standard breakfast or ad libitum lunch.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Pennsylvania Center for Weight and Eating Disorders

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38655793 (View on PubMed)

Other Identifiers

850370

Identifier Type: -

Identifier Source: org_study_id