GLP-1 receptor agonists (e.g., liraglutide, semaglutide, and exenatide) have shown promising effectiveness in treating antipsychotic-induced weight gain, especially for patients on second-generation antipsychotics like olanzapine and clozapine, which are particularly notorious for causing metabolic side effects.
🔍 What the Evidence Shows
1.
Weight Loss Outcomes
- Liraglutide (3.0 mg daily):
- In randomized controlled trials (e.g., Larsen et al., 2017), patients on clozapine or olanzapine lost on average 5–6 kg over 16 weeks compared to placebo.
- Semaglutide (weekly):
- Data is more recent but even more promising. Small trials and case studies report >10% body weight loss over 6 months in some patients.
- Exenatide (twice daily):
- Older studies showed modest weight loss (2–4 kg) and improved glucose metabolism.
2.
Metabolic Improvements
- GLP-1 RAs significantly improve:
- Insulin sensitivity
- Fasting glucose and HbA1c
- Lipid profiles
- These effects are particularly relevant in patients at risk for metabolic syndrome due to antipsychotics.
3.
Safety and Tolerability
- Generally well tolerated. Nausea and GI upset are common at the start but often diminish.
- No significant worsening of psychiatric symptoms has been observed, although close monitoring is essential.
🧠 Mechanism of Benefit
GLP-1 RAs:
- Suppress appetite via central hypothalamic pathways
- Slow gastric emptying
- Improve glucose metabolism and insulin secretion
This mechanism is independent of dopaminergic or serotonergic systems, making GLP-1 agonists safe to combine with most antipsychotics.
📌 Clinical Use Summary
|
Drug |
Route |
Frequency |
Weight Loss (avg) |
Notes |
|
Liraglutide |
Subcutaneous |
Daily |
56 kg (16 wks) |
Good evidence for antipsychotic-induced weight gain |
|
Semaglutide |
Subcutaneous |
Weekly |
>10% body weight |
Emerging as most potent; long-term adherence easier |
|
Exenatide |
Subcutaneous |
Twice daily |
24 kg |
Older agent, less used now |
💡 Conclusion
GLP-1 drugs, especially semaglutide and liraglutide, are effective and safe for managing antipsychotic-induced weight gain, offering clinically meaningful weight loss and metabolic improvements. They may represent a paradigm shift in treating this difficult side effect when lifestyle changes alone are insufficient.
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