King's College London

The research, published in JAMA Psychiatry, provides reassurance that use of GLP1-RAs, such as semaglutide, are not associated with any increased risk of psychiatric adverse events or worsening of depressive symptoms.

People living with obesity and/or diabetes are at an increased risk of poor mental health such as depression. This can have a knock-on impact, resulting in lower adherence to physical health medications, poor control of their blood sugar levels, and an increased risk of health complications related to obesity and diabetes. While there have been some concerns raised by health agencies about the potential negative psychological impact of GLP1-RAs, these reports have been inconsistent.

Researchers in this study identified 80 double-blind placebo-controlled randomised control trials representing 107,860 patients experiencing obesity and diabetes to examine their mental health outcomes, mental health related quality of life, and risk of psychiatric adverse events as a result of GLP1-RA use.

When analysing the data, researchers found that use of GLP1-RA was not associated with a significant difference in risk of serious or non-serious psychiatric adverse events1, nor a change in depression symptoms compared to placebo. However, it was associated with improvements in mental health-related quality of life, restrained eating, and emotional eating behaviors.

Dr Toby Pillinger, an Academic Clinical Lecturer at King’s IoPPN and the study’s senior author said, “Living with obesity and diabetes can take a significant toll on both physical and emotional well-being. Our analysis of data from a large number of clinical trials shows that GLP-1RAs are not only safe from a psychiatric perspective but may improve mental health outcomes. As the use of these medications continues to grow, our findings provide important reassurance to patients and clinicians alike that these treatments can support both body and mind.”

 

Glucagon-like Peptide 1 Receptor Agonsists and Mental Health: A Systematic Review and Analysis (DOI10.1001/jamapsychiatry.2025.0679) (Aureliane C.S. Pierret, Yuya Mizuno, Pippa Saunders, Eshaya Lim, Riccardo Dr Giorgi, Oliver Howes, Robert McCutcheon, Barbara McGowan, Piya Sen Gupta, Daniel Smith, Khalida Ismail, Toby Pillinger) was published in JAMA Psychiatry. 

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