GLP-1 Analogue Effects on Food Cues, Stress, Motivation for Highly Palatable Foods, and Weight

To examine response to a glucagon-like peptide-1 analogue vs. placebo in patients with obesity and assess impact on craving, hunger, stress, and weight outcomes.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: GLP-1 analogue - semaglutide; Other: Placebo

Detailed Description

A randomized, double-blind, placebo-controlled 12-week study with GLP-1 analogue (semaglutide) in men and women with obesity (BMI 30-49.9 kg/m2) in a validated laboratory model to identifying processes underlying greater food craving, intake and weight change, in order to test mechanisms by which a GLP-1 analogues may exerts significant weight effects in obesity.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • The Yale Stress Center: Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI ranging from 30-49.9 kg/m2
• No significant medical problems, including diabetes
• No history of HgbA1c <6.5%
• English speaking and able to read English and complete study evaluations
• Able to provide informed written and verbal consent

Exclusion Criteria:

• Any significant current medical conditions, including neurological, renal, thyroid, cardiovascular, liver, endocrine or immune conditions, including diagnosis of T2DM or T1DM by American Diabetes Association (ADA) criteria
• Meet current or past DSM-IVR criteria for alcohol dependence or any substance use disorders, including nicotine, or psychiatric disorders, including eating disorders, or use of any psychiatric medications, including anxiolytics, antidepressants, naltrexone or antabuse, anti-smoking medications
• Current active participation in a weight loss program or weight loss of >10% of total body weight during the prior 6 months
• Taking any other anti-obesity medication
• History of pancreatitis, medullary thyroid cancer, or MEN syndrome, or (6) women who are pregnant or lactating, or peri/postmenopausal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLP-1a; GLP-1a Semaglutide target dose of 1.2 mg administered weekly over 12 weeks	Drug: GLP-1 analogue - semaglutide; GLP-1 analogue - semaglutide - administered once weekly for a total of 12 weeks; Other Names: Semaglutide
Placebo Comparator: Placebo; Placebo pen administered weekly over 12 weeks	Other: Placebo; Placebo - administered once weekly for a total of 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Craving Score	Change in craving score will be measured using a validated and revised questionnaire called Food Craving Inventory (FCI-R). FCI-R is an 28-item questionnaire that measures how often participants experienced specific food cravings for each of 28 different food types. Participants can respond to each item from "not at all" (score=1) to "more than ever" (score=5), with total FCI-R score range of 28-140. Higher mean scores indicate greater average food craving. A negative change indicates a decrease in craving with treatment.	Average change in avg FCI craving score from week 0 to end of treatment (week 12) computed as avg FCI score at week 12 - avg FCI score at Week 0.
Change in Hunger Score	Hunger will be measured in a Visual Analog Scale (VAS) range from 0 to 10. Higher VAS indicates greater hunger. Negative change in score indicates less hunger with treatment.	Average change in hunger VAS rating from week 0 and end of study week 12 (week 12 VAS - Week 0 VAS)
Change in Food Intake	Food intake will be measured in total calorie energy density during a validated observed laboratory task called the Food Snack Test (FST).Negative change indicates a lower food intake with treatment.	Change in FST total calorie energy density (totalcalED)from FST at week 0 and FST during treatment at week 12 (week 12 FST - Week 0 FST totalcalED change)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Food Intake - Real-World	Food intake will be measured in Kcalories using 3-day 24hr recall (ASA24). A negative change indicates lower food intake with treatment.	Average change from baseline to end of treatment (Kcalories at week 12 - week 0)
Change in Stress Score	Stress, measured as total summed score on the 14-item Perceived Stress Scale, with higher scores indicating greater subjective stress. A negative change indicates lower stress with treatment. The Perceived Stress Scale (PSS)-14 has a total score range of 0 to 56, with individual items scored from 0 ("Never") to 4 ("Very often") and positively worded items reverse-scored before summing.	Average change in stress score from week 0 to end of treatment week 12 (Week 12 - Week 0)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weight	Percent change in Weight in kilograms will be assessed using a bioimpedance scale. higher negative score indicates greater change with treatment.	Average Weight Change from baseline week 0 to end of treatment week 12 (Week 12 - week 0)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Ania Jastreboff, MD, PhD, Internal Medicine (Endocrinology) and Pediatrics (Pediatric Endocrinology);; Principal Investigator: Rajita Sinha, PhD, Psychiatry; Director Yale Stress Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): November 19, 2024

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: 2000027868; 2R01DK099039-06 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes