Thursday, June 5, 2025

How effective are the GLP-1 drugs to treat antipsychotic-induced weight gain? （ChatGPT, 2025-6-5)

 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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