Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis including randomized controlled trials and observational studies
PubMed 42584177 · doi:10.1111/cob.70105
What was done
A systematic review and meta-analysis following PRISMA 2020 guidelines searched biomedical databases, clinical trial registries, pharmacovigilance databases, conference abstracts, and grey literature through January 2026. Included studies were randomized controlled trials, observational studies, database analyses, and pharmacovigilance disproportionality analyses assessing patients receiving semaglutide. Risk of bias was evaluated using ROBINS-I and the Newcastle-Ottawa Scale.
What was found
Compared with comparator or placebo groups, semaglutide was not associated with statistically significant increases in psychiatric outcomes: - Depression pooled risk ratio: 1.25 (95% CI: 0.95-1.65; I² = 98%) - Anxiety pooled risk ratio: 1.22 (95% CI: 0.93-1.60; I² = 99%) - Suicidal ideation/attempt pooled risk ratio: 1.20 (95% CI: 0.90-1.62; I² = 92%)
Why it matters
These findings provide preliminary reassurance that semaglutide does not substantially elevate depression, anxiety, or suicide risk across available trial and real-world safety data.
Limits
The abstract does not state the total number of studies or patients included. The evidence is limited by massive statistical heterogeneity (I² = 92% to 99%), risk of bias, and heavy reliance on spontaneous pharmacovigilance reporting systems.
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