Sema

Active not recruitingPhase NA

Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity

Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity for Metformin Non-responders: a Single-blind Randomized Control Trial

Lead sponsor

Centre for Addiction and Mental Health

Asset

Semaglutide

GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

estimated

Study population

Obesity / overweight, Psychiatric (schizophrenia / bipolar / depression)

Key I/E criterion

•BMI ≥30

Primary endpoint

•Body weight, % change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05333003

Org study ID139/2020

Timeline

Milestones

Study first posted2022-04-18actual

Study start2022-05-25actual

Last update posted2026-05-27actual

Primary completion2026-08estimated (month precision)

Study completion2026-08estimated (month precision)

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Obesity / overweightPsychiatric (schizophrenia / bipolar / depression)

Eligibility

Who can enroll

Minimum age18 Years

Maximum age70 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Stable outpatients or inpatients aged 18-70 years, diagnosed with schizophrenia spectrum disorder, or major depressive disorder with psychotic features, or bipolar disorder (does not need to have psychotic features)

•On maintenance treatment with an AP (stable dose for ≥3 months)

•BMI must be ≥30 kg/m2, OR ≥27 kg/m2 with the presence of at least one weight-related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnea, or impaired fasting glucose, OR BMI ≥25 with individual having gained >5% bodyweight in association with AP treatment

•History of either failure to tolerate metformin or failure to lose ≥5% body weight over at least 16 weeks on the highest tolerated trial of metformin, and who are not currently being treated with metformin (minimum of 1 week metformin-free prior to study entry)

Exclusion criteria

•Patients with severe substance disorder other than tobacco or caffeine use disorder; only severe substance use disorder is exclusionary for cannabis use

•Liver, or renal dysfunction

•A positive drug urine screen other than cannabis as per PI discretion

•Sexually active females of child-bearing age not on a regular contraceptive, or nursing or with a positive pregnancy test

•Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, haematological, or pulmonary disease

•History of reactive hypoglycaemia

•Treatment within 3 months, or failure to tolerate GLP-1RA

•Type 1 Diabetes (T1D) or current diagnosis of Type 2 Diabetes (T2D), diagnosis of T2D on OGTT screen, or HbA1c > 6.5%

•Use of Health Canada approved weight-lowering agents, warfarin, coumarin derivatives, or medication with significant renal impact

•Major medical or surgical event within the preceding 3 months

•Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome

•History of pancreatitis or elevated amylase on screen

•History of severe gastrointestinal disease, (i.e. gastroparesis)

•Acute suicidal risk

•Uncompensated thyroid disorder

•History of heart rhythm disturbances, conduction system abnormalities, or evidence of clinically relevant abnormalities on screening ECG.

•Any condition that interferes with the safe acquisition of MRI data such as metal implants, pacemakers, aneurysm clips, cochlear implants (only for the MRI component; can participate in the remainder of the trial)

•History of gallstones with intact gallbladder or those at increased risk of gallbladder complications (with intact gallbladder)

Endpoints (22)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Patient-reported / QoL

Other clinical outcomes

Weight & body composition

Other (unclassified)

Glycemic / diabetes

Cardiometabolic biomarkers

Weight & body composition

4 endpoints

Primary/protocol endpoint

Weight change

Time frame:32 weeks

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Body Mass Index (BMI)

Time frame:32 weeks

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Waist circumference

Time frame:32 weeks

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Visceral and hepatic adiposity

Time frame:32 weeks

Visceral fat, change

change from baseline, improvement

Glycemic / diabetes

1 endpoint

Secondary/protocol endpoint

Oral glucose tolerance test

Time frame:32 weeks

Postprandial glucose

change from baseline, improvement

Cardiometabolic biomarkers

1 endpoint

Secondary/protocol endpoint

Fasting lipid profile

Time frame:32 weeks

descriptive, improvement

Patient-reported / QoL

7 endpoints

Secondary/protocol endpoint/low confidence

Psychopathology - Brief Psychiatric Rating Scale (BPRS)

Time frame:32 weeks

descriptive, improvement

Secondary/protocol endpoint

Psychopathology - Calgary Depression Scale for Schizophrenia (CDSS)

Time frame:32 weeks

change from baseline, improvement

Secondary/protocol endpoint

Psychopathology - Global Assessment of Functioning (GAF)

Time frame:32 weeks

change from baseline, improvement

Secondary/protocol endpoint

Psychopathology - Clinical Global Impression scale (CGI)

Time frame:32 weeks

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Lifestyle assessment - Assessment of Quality of life (AQoL)

Time frame:32 weeks

descriptive, improvement

Secondary/protocol endpoint

Lifestyle assessment - WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)

Time frame:32 weeks

descriptive, improvement

Secondary/protocol endpoint

Lifestyle assessment - Food Cravings Questionnaire (FCQ)

Time frame:32 weeks

descriptive, improvement

Other clinical outcomes

6 endpoints

Secondary/protocol endpoint

Change in cognitive performance

Time frame:32 weeks

change from baseline, improvement

Secondary/protocol endpoint

Lifestyle assessment - The Fagerstrom Test of Nicotine Dependence (FTND)

Time frame:32 weeks

change from baseline, improvement

Secondary/protocol endpoint

Lifestyle assessment - Penn State Nicotine Dependence Index-Cigarette/Electronic Cigarette

Time frame:32 weeks

descriptive

Secondary/protocol endpoint

Lifestyle assessment - Canadian Diet History Questionnaire II (C-DHQ II)

Time frame:32 weeks

descriptive

Other/protocol endpoint/low confidence

Structural MRI

Time frame:32 weeks

descriptive

Other/protocol endpoint/low confidence

Arterial spin labeling (ASL)

Time frame:32 weeks

descriptive

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

Lifestyle assessment - International Physical Activity Questionnaire (IPAQ)

Time frame:32 weeks

descriptive

Other/protocol endpoint/low confidence

Resting state functional MRI (rsfMRI)

Time frame:32 weeks

descriptive

Other/protocol endpoint/low confidence

1H-Magnetic resonance spectroscopy (MRS)

Time frame:32 weeks

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.