Brain Plasticity and GLP-1 Receptor Agonist Treatment for Obesity

What Was Tested

This registered phase 3 trial tested Semaglutide.

Glucagon-like peptide 1 receptor agonists (GLP-1RA), such as Ozempic and Wegovy, have been rapidly adopted for the treatment of obesity in both youth and adults.

However, despite this rapid adoption and the known GLP-1RA mechanism of action for weight loss, which targets brain circuits responsible for appetite and eating behaviors, almost nothing is known about how these drugs affect the brain in youth who are treated for obesity, or how these drugs affect the brain of youth differently from adults.

The goal of the current study is to compare youth and adults with obesity who are treated a GLP-1RA and measure potential difference in GLP-1RA associated change in brain function, appetite, and eating behaviors.

It had six arms (groups): Pubertal Adolescent - Continuous Treatment (experimental), Pubertal Adolescent - Early Treatment Cessation (experimental), Post-Pubertal Adolescent - Continuous Treatment (experimental), Post-Pubertal Adolescent - Early Treatment Cessation (experimental) and Adult - Continuous Treatment (active comparator).

Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 32 weeks of semaglutide (s.c.).

Pubertal adolescents defined as Tanner stage 2-4 and/or 12-15 y/o who will receive 24 weeks of semaglutide (s.c.) followed by 8 weeks of placebo.

Post-pubertal adolescents defined as Tanner stage 5 and/or 16-18 y/o who will receive 32 weeks of semaglutide (s.c.).

The registry classes the interventions as drug.

Who Took Part

Enrollment: 120 planned participants were the target.

It was open to people of any sex aged from 12 years up to 45 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Male or female (sex assigned at birth). 30-45 y/o with obesity (BMI\>35 kg/m2).

The full record lists 4 inclusion and 9 exclusion criteria; among the exclusions: treated with glucagon-like peptide-1 (glp-1) agonists (e.g., exenatide, liraglutide, semaglutide, tirzepatide) for weight management in the prior 3 months; currently taking anti-psychotic medications (anti-depressants accepted); diagnosis of type 2 diabetes.

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

The participants were allocated by chance, so the Semaglutide group and the comparison group should start out alike.

The Semaglutide group and the comparison group ran side by side rather than switching.

As a double-blind Semaglutide study, the assignments were hidden from both participants and investigators until the end.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-06-15 with completion listed for 2031-04-30.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): blood oxygen-level dependent signal (time frame: From enrollment to the end of trial at 32 weeks). meal kilocalories (kcal) (time frame: From enrollment to the end of trial at 32 weeks). visual analogue scale (VAS) score for hunger (time frame: From enrollment to the end of trial at 32 weeks).

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Semaglutide in 120 people.

Its status is not yet recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.