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

Prior treatment

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

Other illness

• A diagnosis of type I or II diabetes
• 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
• Known or suspected allergy or hypersensitivity to trial medication(s), excipients, or related products
• Applicants with current severe major depressive disorder (BDI-II score ≥ 29 or Patient Health Questionnaire-9 \[PHQ-9\] score \> 15) or severe anxiety disorder
• Any severity of psychotic or bipolar disorder
• 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.)
• 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:

Lab values

• Hemoglobin A1c (HbA1c) \> 6.5%

Other

• 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)
• 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
• complete a week 60 assessment

• 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.