Efficacy and safety of GLP-1 receptor agonists for antipsychotic-related overweight and metabolic dysregulation: a systematic review and meta-analysis.
Lingyan Zhou, Ying Zhang, Chao Shen et al.
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In 30 seconds
This systematic review and meta-analysis pooled randomized controlled trials of GLP-1 receptor agonists in adults receiving antipsychotic treatment for overweight or metabolic dysregulation. Across eight trials involving 535 randomized participants, treatment was associated with lower body weight than control (mean difference −6.54 kg, 95% CI: −9.80 to −3.29; P < 0.001), alongside improvements in BMI and HbA1c. Nausea, vomiting, and constipation were more frequent, while serious adverse events and discontinuation outcomes did not differ significantly. Psychiatric adverse events were too infrequent for pooled analysis, leaving psychiatric safety uncertain.
Key findings
- Body weight was lower with GLP-1RAs (MD = -6.54 kg, 95% CI: -9.80 to -3.29, P < 0.001, I 2 = 92%).
- BMI and HbA1c also decreased (MD = -2.34 kg/m 2 and MD = -0.32%, respectively; both P < 0.001).
- Nausea, vomiting, and constipation risks were higher (RR = 1.61, 2.10, and 2.34, respectively).
- Psychiatric adverse events were infrequent and could not be pooled; psychiatric safety therefore remains uncertain.
Why it matters
Antipsychotic-associated weight and metabolic changes can be clinically important, and these pooled trial results suggest GLP-1RAs may improve weight-related and glycemic measures in this population. The accompanying increase in gastrointestinal adverse events is relevant to tolerability, while sparse psychiatric safety data mean the overall benefit–risk profile is not fully established.
What to keep in mind
The evidence comprised eight trials with substantial heterogeneity for weight and BMI outcomes. Psychiatric adverse events were too infrequent to pool, and the authors call for longer-term trials with standardized safety reporting.