Ozempic (Semaglutide) for Antipsychotic-Induced Weight Gain
Ozempic (semaglutide) can be used off-label to treat antipsychotic-induced weight gain, though metformin remains the first-line pharmacological intervention recommended by guidelines. 1
First-Line Approach: Metformin
Metformin should be offered concomitantly with antipsychotics that have poor cardiometabolic profiles to attenuate potential weight gain. 1 The recommended starting dose is 500 mg once daily, gradually increasing to 1g twice daily as tolerated. 1 Modified-release preparations should be used when available to minimize gastrointestinal side effects. 1
- Metformin achieves approximately 3% weight loss, with 25-50% of participants achieving at least 5% weight loss. 2
- Doses greater than 1500 mg are associated with the greatest weight loss. 2
- Metformin is frequently offered to mitigate weight gain due to antipsychotic medication, though not FDA approved for this specific indication. 2
- Before starting metformin, assess renal function as it should be avoided in patients with renal failure. 1
- Ongoing monitoring should include annual liver function, HbA1c, renal function, and vitamin B12. 1
GLP-1 Receptor Agonists (Including Ozempic)
While not FDA-approved for antipsychotic-induced weight gain, GLP-1 receptor agonists may be considered as an additional pharmacological option. 1 Recent evidence demonstrates their effectiveness:
- In a large retrospective cohort study (n=66,574), patients prescribed incretin-based medications (semaglutide and tirzepatide) lost -2.17 kg and were 1.71 times more likely to achieve 5% weight loss compared to those without prescriptions. 3
- Effectiveness varies by antipsychotic category: Weight loss was greater among those prescribed low weight-gain-risk antipsychotics (-3.02 kg) compared to high weight-gain-risk antipsychotics like olanzapine and clozapine (-1.33 kg). 3
- Medications commonly used off-label for obesity include Ozempic (semaglutide injection), though health insurance coverage may be restricted to FDA-approved indications (diabetes). 2
Important Caveats
- Ozempic is less effective in patients taking high-risk antipsychotics (olanzapine, clozapine) compared to lower-risk agents. 3
- Medicare currently excludes coverage of FDA-approved anti-obesity medications for obesity diagnosis alone, and these medications are often costly. 2
- Global shortages of GLP-1 receptor agonists currently exist. 2
Antipsychotic Selection Strategy
The most effective strategy for prevention of weight gain is choosing antipsychotics with low weight gain liability when clinically appropriate. 1, 4
- Lurasidone and ziprasidone appear to be the most weight-neutral options. 1
- Aripiprazole demonstrates lower risk for weight gain. 1
- Olanzapine, clozapine, quetiapine, and risperidone are consistently associated with significant weight gain. 1
Monitoring Protocol
Before starting antipsychotic treatment, obtain baseline measurements of BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram. 1
- Recheck fasting glucose 4 weeks after initiation. 1
- Monitor BMI, waist circumference, and blood pressure weekly for the first 6 weeks. 1
- Repeat all baseline measurements after 3 months of treatment and annually thereafter. 1
Non-Pharmacological Interventions
Lifestyle interventions should be implemented for all patients on antipsychotics, including dietary counseling and promotion of physical activity. 1 These remain essential regardless of pharmacological approach chosen.