Semaglutide for Schizophrenia and Obesity

(Sema Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Margaret Hahn, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Must not be taking: GLP-1RA, Weight-lowering agents

Disqualifiers: Severe substance disorder, Diabetes, others

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a medication to help overweight or obese patients with schizophrenia who are on antipsychotics and haven't lost enough weight with metformin. The medication works by making you feel full sooner and helping your body use insulin better. It has been shown to induce significant weight loss in individuals with obesity or overweight.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on metformin for at least one week before joining. You also need to be on a stable dose of antipsychotic medication for at least three months.

What data supports the effectiveness of the drug semaglutide for schizophrenia and obesity?

Research shows that semaglutide, a drug approved for type 2 diabetes and obesity, may help reduce weight gain associated with antipsychotic medications in patients with severe mental illness. In a study, patients who did not respond to metformin experienced significant weight loss after using semaglutide, suggesting its potential effectiveness in managing weight in similar conditions. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been studied for its safety in treating obesity and type 2 diabetes, and it is generally well-tolerated with some side effects. In studies, it has shown relatively well-tolerated side effects when used for weight management in people with severe mental illness and those taking antidepressants. ^{1 2 3 6 7}

How is the drug semaglutide unique for treating schizophrenia and obesity?

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (a type of drug that mimics a hormone involved in blood sugar control) that is administered once a week and has shown promise in managing weight gain associated with antipsychotic medications, which is a common issue in schizophrenia treatment. Unlike other treatments, it offers significant weight loss and cardiovascular benefits, making it a novel option for patients with both schizophrenia and obesity. ^{1 2 3 8 9}

Research Team

Margaret Hahn, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

This trial is for adults aged 18-65 with schizophrenia spectrum disorder or related conditions, who are obese due to antipsychotic medications and haven't lost weight on metformin. Participants must have a BMI of at least 30, or 27 with certain health issues, and can't be pregnant, nursing, or without contraception if applicable.

Inclusion Criteria

My BMI is over 30, or over 27 with a weight-related health issue, or over 25 and I've gained more than 5% of my weight due to AP treatment.

I have been on a stable dose of antipsychotic medication for over 3 months.

I am 18-65 years old with schizophrenia, major depression with psychosis, or bipolar disorder.

Exclusion Criteria

I have diabetes, with an HbA1c level over 6.5%.

You have a serious addiction to drugs or alcohol, except for tobacco or caffeine. Only severe addiction to cannabis would exclude you from participating.

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)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive semaglutide or placebo on a weekly schedule, with adherence tracked

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Semaglutide (GLP-1 Receptor Agonist)

Trial Overview The study tests whether semaglutide helps overweight individuals with schizophrenia spectrum disorders lose weight compared to a placebo. These patients struggle with obesity partly because of their antipsychotic medication and haven't had success losing weight on metformin.

Participant Groups

Group I: Semaglutide Experimental Treatment 1 Intervention

Semaglutide medication will be taken by participants on a weekly schedule, and adherence tracked

Group II: Placebo Placebo Group 1 Intervention

Placebo will be taken by participants on a weekly schedule, and adherence tracked

Semaglutide is already approved in Canada, Japan for the following indications:

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Dr. Catherine Zahn

Centre for Addiction and Mental Health

Chief Executive Officer since 2009

MD, University of Toronto

Dr. James Graham

Centre for Addiction and Mental Health

Chief Medical Officer since 2024

PhD in Functional Neuroimaging

Findings from Research

In a study of 12 patients with severe mental illness who did not respond to metformin for antipsychotic-associated weight gain, semaglutide treatment resulted in significant weight loss over 12 months, averaging 8.67 kg (p=0.04).

Semaglutide was well-tolerated with manageable side effects, suggesting it could be a promising alternative for patients struggling with weight gain from antipsychotic medications, although further randomized control trials are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series. Prasad, F., De, R., Korann, V., et al.[2023]

This study will evaluate the long-term effects of semaglutide, a medication approved for type 2 diabetes and obesity, as an add-on treatment for patients with schizophrenia who are taking clozapine or olanzapine, focusing on its impact on metabolic health over 26 weeks.

With 104 participants aged 18-65, the trial aims to measure changes in HbA1c levels, body weight, and various metabolic markers, providing insights into whether semaglutide can mitigate the weight gain and metabolic disturbances associated with these antipsychotic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry). Sass, MR., Danielsen, AA., Köhler-Forsberg, O., et al.[2023]

Semaglutide 2.4 mg led to significant weight loss in adults with overweight/obesity, achieving a mean change of -15.7% for those on antidepressants compared to -0.2% for placebo, demonstrating its efficacy regardless of antidepressant use.

The safety profile of semaglutide was consistent with previous studies, showing a similar prevalence of adverse events between the semaglutide and placebo groups among participants taking antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis. Kushner, RF., Fink-Jensen, A., Frenkel, O., et al.[2023]

In a pilot trial involving 47 participants with schizophrenia or related disorders, liraglutide 3.0 mg daily led to a significant average weight loss of 5.7 kg over 6 months, compared to no significant change in the placebo group.

The study demonstrated good retention rates, with 79% of participants completing the trial, indicating that liraglutide is a feasible and acceptable option for managing obesity in individuals with severe mental illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis: Results of a pilot randomized, double-blind, placebo-controlled trial. Whicher, CA., Price, HC., Phiri, P., et al.[2022]

In a meta-analysis of 164 patients with schizophrenia, glucagon-like peptide-1 receptor agonists (GLP-1RAs) led to a significant body weight loss of 3.71 kg compared to controls after about 16 weeks, particularly benefiting those treated with clozapine or olanzapine.

While GLP-1RAs were effective in reducing weight and improving metabolic markers, they were associated with a higher incidence of nausea compared to controls, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: A systematic review and individual participant data meta-analysis. Siskind, D., Hahn, M., Correll, CU., et al.[2019]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective for treating type 2 diabetes and obesity, providing significant weight loss and cardiovascular benefits, making it crucial for high-risk patients.

However, during the SUSTAIN clinical trial program, a safety concern arose regarding the worsening of diabetic retinopathy, potentially linked to rapid reductions in HbA1c levels, which requires further investigation and careful clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. Cigrovski Berkovic, M., Strollo, F.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

The use of liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis: Results of a pilot randomized, double-blind, placebo-controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: A systematic review and individual participant data meta-analysis. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. [2023]