TOPLINE

The use of semaglutide was not associated with an increased risk for depression compared with placebo or other antidiabetic/antiobesity agents, but the evidence was limited and of very low certainty. 

METHODOLOGY

• Researchers conducted a systematic review and meta-analysis to assess whether semaglutide was associated with increased risk for depression in people treated for overweight, obesity, or type 2 diabetes.
• They searched major databases, trial registries, pharmacovigilance sources and grey literature through January 2026. The final analysis included five studies including two pharmacovigilance studies, two retrospective cohort studies, and a post hoc analysis of randomized trials.
• Studies compared semaglutide with placebo or other GLP-1 drugs, or other anti-obesity or anti-diabetic drugs. Some evidence came from pharmacovigilance reports. 
• The primary outcome was the risk for depression. Secondary outcomes included anxiety disorders/symptoms, suicidal ideation/attempts, and composite psychiatric outcomes.
• Certainty of evidence and heterogeneity (I²) were assessed.

TAKEAWAY

• No significant association was found between semaglutide use and depression risk compared with control groups (four studies; I² = 98%).
• The use of semaglutide was not associated with significant differences in risk for anxiety (four studies; I² = 99%) or suicidal ideation/attempt (three studies; I² = 92%).
• The certainty of evidence for depression, anxiety, and suicidal ideation/attempt was judged to be very low.

IN PRACTICE

"Be­cause the evidence base is limited, heterogeneous and partly derived from spontaneous-reporting systems, these findings should be interpreted cautiously. Clinicians should continue routine baseline assessment and follow-up monitoring for psy­chiatric symptoms, particularly in patients with pre-existing psychiatric vulnerability," the authors of the study wrote.

SOURCE

The study was led by Gaurab Bhaduri, Park View Super Speciality Hospital in Kolkata, India. It was published online on August 12 in Clinical Obesity.

LIMITATIONS

The analysis included a small number of studies. The included studies showed substantial statistical heterogeneity. Part of the evidence was derived from spontaneous‑reporting pharmacovigilance systems.

DISCLOSURES

The authors did not report any funding. The authors declared having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.