Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity

Prior treatment

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

Other illness

• Patients with severe substance disorder other than tobacco or caffeine use disorder; only severe substance use disorder is exclusionary for cannabis use
• History of reactive hypoglycaemia
• Treatment within 3 months, or failure to tolerate GLP-1RA
• 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)
• 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)

Lab values

• Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, haematological, or pulmonary disease
• Type 1 Diabetes (T1D) or current diagnosis of Type 2 Diabetes (T2D), diagnosis of T2D on OGTT screen, or HbA1c \> 6.5%

Age

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

Other

• Liver, or renal dysfunction
• Acute suicidal risk

• 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)