The Joule MARS study is a single center, randomized, open label clinical trial aiming to explore the metabolic adaptations that occur in response to weight management in adolescents with obesity. Behavioural lifestyle intervention with and without a pharmacological intervention - semaglutide- will be studied. Study participants will be randomized to one of two groups. Group A will follow a behavioral lifestyle program (BLP) alone for 6 months, followed by BLP and treatment with semaglutide for six months. Group B will be enrolled in BLP and semaglutide from baseline to 6 months. The primary research question will assess, in youth aged 12-17 years diagnosed with obesity and enrolled in a weight management program, if the implementation of a BLP together with semaglutide, compared to the implementation of BLP alone for 6 months leads to less adaptive thermogenesis.

The Joule MARS (Metabolic Adaptation to weight loss in Response to a behavioural lifestyle program with or without Semaglutide in adolescents with obesity) study is a single-center, randomized controlled trial designed to investigate the effects of a behaviour lifestyle program and the medication semaglutide on resting energy expenditure (REE), work efficiency during standard exercise on a cycle ergometer and related metabolic outcomes in adolescents with obesity. The study will involve two intervention groups:

Group A will participate in a behavioral lifestyle program (BLP) alone for 6 months followed by a combination of semaglutide treatment and a BLP for an additional 6 months.

Group B will receive semaglutide and a BLP for the first 6 months and then terminate the study.

The study objectives are to determine if, in youth aged 12-17 years with obesity and enrolled in a weight management program:

1. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone leads to less adaptive thermogenesis (AT) at 6 months;

2. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone for 6-month, leads to:

   Less increase in energy work efficiency during standardized exercise

   Differences in BAT activity

   Differences in health-related quality of life (HRQoL)

3. BLP and semaglutide, compared to BLP alone, lead to improvements in metabolic health measures (including lipids, glycemia, liver enzymes, hepatic fat and hepatic stiffness) after 6 months.

4. A longer time enrolled in BLP prior to addition of 6 months of semaglutide alters health outcome response to semaglutide.

A comprehensive assessment will be conducted throughout the study. Using whole-room indirect calorimetry, REE and muscle work efficiency, evaluated during standardized physical activity on a cycle ergometer, will be measured. Body composition (Dual energy x-ray absorptiometry and bioelectric impedance analysis), anthropometry (height, weight, waist circumference, BMI, BMI z score (WHO)), metabolic health, health related quality of life, hepatic fat and cold induced brown adipose tissue activity (MRI) will be assessed. Randomization will be managed via the REDCap EDC system.

Inclusion Criteria:

• Youth aged 12-17 years
• Diagnosed with obesity (BMI ≥2 standard deviations above WHO Reference median)
• Enrolled in Growing Health Weight Management or Next Step pediatric clinics (ie. have at least one year of the program remaining).

Exclusion Criteria:

• Any contraindications for MRI (i.e. claustrophobia, implanted metal, metallic injuries recent tattoo or weight >300lb. Ineligible for imaging visit only.
• Use of atypical anti-psychotics.
• Use of the following medication classes: (i.e. Beta-blocker medications, Steatogenic medications, Anti-hyperglycemic medications, HIV drugs, Antidepressants, anxiolytic drugs, anti-psychotic drugs, Thyroid drugs, Antiemetic or amphetamine, dextromethorphan and metoclopramide.)
• Elevated alanine aminotransferase (ALT) > 5 x upper range of normal at screening.
• Use of glucose lowering or any anti-obesity medication in the previous 3 months.
• Known monogenic, syndromic or hypothalamic causes of obesity.
• Diagnosis of type 1 or 2 diabetes mellitus.
• Prior bariatric surgery or liver transplantation.
• Alcohol intake exceeding 3 drinks per week or reported cannabis use.
• Recent history of cigarette smoking (previous 3 months) - ineligible for imaging only.
• History or family history of multiple endocrine neoplasia 2 or medullary thyroid cancer.
• History of pancreatitis.
• Presence of untreated endocrine disorder.
• History of an eating disorder and / or history of suicidal ideation
• History of a cardiac condition that precludes exercise testing or unable to have exercise testing done in the GHWM pediatric clinic, inability to use a cycle ergometer.

Participant who does not have a peak power value obtained in the GHWM pediatric clinic

Female who is pregnant, breast-feeding or intends to become pregnant.

Female who refuses to use a means of contraception if sexually active.

Participation in any interventional clinical study within 90 days before screening.