Physiologic Response to Bariatric Surgery and the Impact of Adjunct Semaglutide in Adolescents

Observation Phase

Inclusion Criteria:

- Signed and dated informed consent form

- Willingness to comply with all study procedures and availability for the duration of
the study

- Male or female biological sex, age 12 through 24 years

- In the preoperative pathway for vertical sleeve gastrectomy

Exclusion Criteria:

- Planned Roux-en-Y gastric bypass

- Hypothalamic obesity

- Type 2 Diabetes

- Use of oral glucocorticoids (within 10 days of baseline visit)

- Use of metformin (within 3 months of baseline visit)

- Use of insulin secretagogues (within 4 half-lives of the medication of baseline
visit)

- Current use of insulin

- Use of anti-obesity medications (within 4 half-lives of the medication of baseline
visit)

Intervention/Treatment Phase

Inclusion Criteria:

- Signed and dated informed consent form

- Status post vertical sleeve gastrectomy

- Male or female biological sex, age 12 through 24 years

- Meeting minimum nutrition goals

- Obesity: age 12-17 years: BMI ≥95th%ile for age/sex | age 18-24 years: BMI ≥
30kg/m^2

- If entering the Intervention phase from the Observational phase: ≤20% BMI loss at 1
year postop

- If entering the Intervention phase from the existing patient pool: ≤20% BMI loss at
1-2 years postop

Exclusion Criteria:

- Surgically correctable cause of suboptimal postoperative weight loss

- Known hypersensitivity to any component of semaglutide

- Personal or family history of medullary thyroid carcinoma

- Personal history of multiple endocrine neoplasia type 2

- Hypothalamic Obesity

- Type 2 Diabetes

- History of pancreatitis

- Uncontrolled hypertension

- Clinically significant arrhythmia or heart disease that could be exacerbated by
increased heart rate

- Malignant neoplasm within the last 5 years

- Untreated thyroid disorder

- Tanner Stage 1

- Baseline alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 5x upper
limit of normal

- Baseline Creatinine >1.2mg/dL

- Active treatment for bulimia nervosa

- Active major psychiatric disorder limiting informed consent

- Suicidal ideation of type 4 or 5 on Columbia-Suicide Severity Rating Scale (C-SSRS)

- Intentional self-harm within the previous 1 month

- Severe unmanaged depression, defined by Center for Epidemiological Studies
Depression (CESD) score of 26 or greater and by clinical evaluation

- Recent change to concomitant medications for hypertension, dyslipidemia, depression
or anxiety (<4 weeks prior to enrollment)

- Use of oral glucocorticoids (within 10 days of baseline visit)

- Use of metformin (within 3 months of baseline visit)

- Use of insulin secretagogues (within 4 half-lives of the medication of baseline
visit)

- Current use of insulin

- Use of anti-obesity medications (within 4 half-lives of the medication of baseline
visit)

- Current pregnancy

- For females of reproductive potential: Plan to become pregnant in the next 8 months

- For females of reproductive potential: Not on contraception (i.e. two forms of birth
control for example oral birth control pills and condoms) for at least 1 month prior
to enrollment and agreement to use these during study participation and for an
additional 8 weeks after the final dose of study medication