Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis

This meta-analysis found no statistically significant increase in depression, anxiety, or suicidal ideation/attempt in people taking semaglutide compared with placebo or comparator groups, though all pooled risk ratios were slightly above 1. The analysis pooled evidence from trials, observational studies, large databases, and pharmacovigilance reports, but high heterogeneity and risk of bias weaken certainty. The authors view the results as reassuring but not definitive proof of no psychiatric risk.

Meta-analysis — Systematic review and meta-analysis. Population: Patients receiving semaglutide for Type 2 diabetes, obesity, or related metabolic conditions. Interventions: semaglutide.

Pooled risk ratios were 1.25 (95% CI: 0.95-1.65; I² = 98%) for depression, 1.22 (95% CI: 0.93-1.60; I² = 99%) for anxiety, and 1.20 (95% CI: 0.90-1.62; I² = 92%) for suicidal ideation/attempt. None of these differences between semaglutide and comparator or placebo groups were statistically significant. The authors report no statistically significant increase in depression, anxiety, or suicidal ideation/attempt, but they emphasize that high heterogeneity, risk of bias, and heterogeneous data sources limit certainty. They frame the findings as absence of a detected increased risk in available evidence rather than definitive proof of no psychiatric risk.

For researchers studying semaglutide, this paper aggregates current evidence on whether the drug is associated with depression, anxiety, or suicidal ideation/attempt. It does not establish psychiatric safety; pooled risk ratios were above 1 but not statistically significant, and the evidence base was heterogeneous. It serves as a cautious reference point for future safety monitoring and hypothesis generation.

Key findings

Pooled risk ratio for depression with semaglutide was 1.25 (95% CI: 0.95-1.65; I² = 98%).
Pooled risk ratio for anxiety was 1.22 (95% CI: 0.93-1.60; I² = 99%).
Pooled risk ratio for suicidal ideation/attempt was 1.20 (95% CI: 0.90-1.62; I² = 92%).
No comparison between semaglutide and placebo or comparator groups reached statistical significance.
Evidence was limited by substantial heterogeneity, risk of bias, and reliance on heterogeneous data sources including spontaneous-reporting studies.

Limitations

Substantial heterogeneity across pooled estimates (I² 92–99%)
Risk of bias in included studies
Reliance on heterogeneous data sources, including spontaneous-reporting and pharmacovigilance studies
Observational and pharmacovigilance components may introduce confounding and reporting bias

The record

Journal: Clinical obesity 16(5): e70105
Published: 2026-08-17
PMID: 42584177 — DOI: 10.1111/cob.70105
MeSH terms: Humans, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Risk Factors, Depression, Glucagon-Like Peptides, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide
Author countries: India

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.