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Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis
Gaurab Bhaduri1,2, Shilanjan Roy3, Anchin Kalia4
1Department of Diabetes & Endocrinology, Park View Super Speciality Hospital, Kolkata, West Bengal, India.
Clinical Obesity
|August 12, 2026
Summary
This review found no significant increase in depression or anxiety for semaglutide users. While reassuring, the evidence has limitations, suggesting no detected psychiatric risk rather than absolute proof.
Area of Science:
- Endocrinology
- Pharmacology
- Psychiatry
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, are key treatments for Type 2 diabetes mellitus (T2DM) and obesity.
- Neuropsychiatric effects of GLP-1RAs, particularly semaglutide, are a subject of ongoing research with inconsistent findings.
Purpose of the Study:
- To systematically review and meta-analyze the risk of depression, anxiety, and suicidal ideation/attempt in patients treated with semaglutide.
- To evaluate the safety profile of semaglutide concerning neuropsychiatric adverse events.
Main Methods:
- Systematic review and meta-analysis following PRISMA 2020 guidelines.
- Searched multiple databases (biomedical, trial registries, pharmacovigilance) and grey literature up to January 2026.
- Included RCTs, observational studies, database analyses, and pharmacovigilance studies; assessed risk of bias using ROBINS-I and Newcastle-Ottawa Scale.
Main Results:
- Pooled risk ratios for depression, anxiety, and suicidal ideation/attempt were 1.25 (95% CI: 0.95-1.65), 1.22 (95% CI: 0.93-1.60), and 1.20 (95% CI: 0.90-1.62), respectively.
- No statistically significant increase in these neuropsychiatric events was observed compared to comparator or placebo groups.
- Substantial heterogeneity (I² > 90%) and risk of bias were noted across studies.
Conclusions:
- Current evidence does not demonstrate a statistically significant increased risk of depression, anxiety, or suicidal ideation/attempt with semaglutide use.
- The certainty of evidence is limited by heterogeneity and data source limitations, indicating an absence of detected risk rather than definitive proof of safety.
- Findings are reassuring but warrant cautious interpretation due to evidence limitations.
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