Semaglutide for antipsychotic weight gain

A research team at Copenhagen University Hospital, Bispebjerg, published the protocol for a new trial on 17 September 2026 that asks a narrow but underexamined question: can weekly semaglutide help adolescents who have gained significant weight while taking antipsychotic medication^[1]. The trial, named GOAL, has not enrolled a single patient's worth of results yet. It is a feasibility study, meaning the question at this stage is whether the trial design works at all, not whether the drug works. That distinction matters for how readers should treat everything below.

Antipsychotic medications treat serious conditions, including psychotic disorders, mood disorders and some neurodevelopmental disorders in young people. A well-documented side effect of many of these drugs is rapid weight gain, and that gain carries its own long-term health cost. Until now, clinicians treating this group have had little trial evidence to guide a pharmacological response.

Why antipsychotic-associated weight gain is a real problem

The scale of the problem was established by a landmark 2009 cohort study in JAMA. Researchers followed 338 antipsychotic-naive children and adolescents in New York starting their first course of a second-generation antipsychotic. After a median of about 11 weeks of treatment, weight increased by 8.5 kg on olanzapine, 6.1 kg on quetiapine, 5.3 kg on risperidone and 4.4 kg on aripiprazole, compared with a change of just 0.2 kg in an untreated comparison group^[2]. Total cholesterol and triglycerides also rose significantly on olanzapine and quetiapine. That data set, now over fifteen years old, is still the reference point clinicians cite when explaining why this population needs a monitored weight-management plan, not just a general recommendation to eat less and move more.

Lifestyle intervention alone has a poor track record in this group. Some antipsychotics affect appetite regulation directly, and many patients are also managing symptoms that make structured diet and exercise programmes harder to sustain. That combination is what has pushed researchers toward testing a GLP-1 receptor agonist (glucagon-like peptide-1 receptor agonist, the drug class that includes semaglutide and works by slowing digestion and reducing appetite signals in the brain) as an add-on to standard psychiatric care.

What the GOAL trial is actually testing

The GOAL trial plans to enrol 34 adolescents aged 12 to 18 with obesity, defined using a body mass index standard-deviation score of at least +1.28 and body fat at or above the 95th percentile for age. All participants must be on stable antipsychotic treatment for a psychiatric diagnosis; the protocol specifically excludes adolescents receiving antipsychotic treatment under coercion^[1]. This is a single-arm, open-label study, meaning every participant receives the same treatment and everyone involved, researchers and participants alike, knows who is getting what. There is no placebo group at this stage.

Participants will receive once-weekly subcutaneous semaglutide, titrated up to 2.4 mg, for 36 weeks on top of their existing psychiatric care, followed by an 18-month observational follow-up period. The primary outcome is not weight loss. It is the study completion rate, the proportion of enrolled adolescents who finish the full 36-week treatment period. Recruitment rate, treatment adherence and completion of study procedures are the other feasibility outcomes the researchers are tracking^[1]. Changes in BMI standard-deviation score, body composition, metabolic biomarkers and psychiatric outcomes are collected as secondary measures, but this trial is not statistically powered to draw firm conclusions from them.

The study is registered in the EU Clinical Trials Information System under number 2024-517471-21-02 and is being run in collaboration with the Child and Adolescent Mental Health Center in Copenhagen. It complies with the Declaration of Helsinki and EU Clinical Trials Regulation 536/2014, and written informed consent is required from both participants and their legal guardians.

What semaglutide has shown in adolescents so far

Semaglutide already carries regulatory approval for adolescent obesity in general, separate from the antipsychotic question. The STEP TEENS trial, published in the New England Journal of Medicine in 2022, randomised 201 adolescents aged 12 to under 18 with obesity or overweight plus a weight-related condition to semaglutide 2.4 mg weekly or placebo, both alongside lifestyle intervention, for 68 weeks. The semaglutide group's BMI fell by a mean of 16.1%, against a 0.6% rise on placebo. Seventy-three percent of the semaglutide group lost at least 5% of their body weight, compared with 18% on placebo^[3]. Gastrointestinal side effects, nausea, vomiting and diarrhoea among them, were more common on semaglutide (62%) than placebo (42%), and cholelithiasis (gallstones) occurred in 4% of the semaglutide group versus none on placebo.

That trial excluded adolescents on antipsychotic medication, which is exactly the gap the GOAL trial is built to address. Antipsychotic-associated weight gain has a different underlying biology than general adolescent obesity in several respects, including the drugs' direct effects on appetite-regulating pathways in the brain, so efficacy and safety data from STEP TEENS cannot simply be assumed to transfer to this population without dedicated testing.

What this trial does not show

Because this is a protocol paper, not a results paper, there is no weight-loss figure to report yet. The trial has not finished enrolling, let alone completed 36 weeks of treatment plus 18 months of follow-up for its participants. Readers should not treat this coverage as evidence that semaglutide works, or is safe, for adolescents on antipsychotic medication. What the protocol establishes is that a structured, ethically approved trial exists to answer that question, and that the researchers designed it explicitly as a feasibility study meant to inform the design of a larger randomised controlled trial later, not to answer the efficacy question itself.

The trial also excludes adolescents whose antipsychotic treatment is administered under coercion, which narrows the population the results, whenever they arrive, will generalise to. And with only 34 participants, the study is sized to test whether the trial can run smoothly, not to detect anything but a large effect on the secondary outcomes.

What this means for readers

If you are a parent or caregiver of a teenager on antipsychotic medication who has gained substantial weight, the honest answer today is that pharmacological options are being studied, but none is yet supported by adolescent-specific trial data in this exact population. Any decision about adding a GLP-1 receptor agonist to a young person's psychiatric care belongs with the prescribing clinician, who can weigh the individual's diagnosis, current medication regimen, and metabolic risk. Denmark's regulatory status for semaglutide, prescription-only, like every other market we track, is on our Denmark regulation page, and the general adolescent evidence base is summarised on the semaglutide peptide page.

This article is for educational and journalistic purposes only and does not constitute medical advice. Semaglutide is a prescription-only medicine in every jurisdiction we track, and its use in adolescents, especially alongside antipsychotic treatment, requires specialist supervision. This is not guidance for self-directed use. Always consult a qualified healthcare professional, ideally one with expertise in pediatric endocrinology or adolescent psychiatry, before considering any change to a young person's treatment plan.