Glucagon-like peptide-1 receptor agonists and risk of depression: a systematic review and meta-analysis
Abstract
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven effectiveness in stimulating weight loss, as well as enhancing metabolic parameters. Nevertheless, the information available on the possible effects on mood and the risk of depression is not consistent, and it is possible that further research should evaluate the psychiatric safety of GLP-1RA usage. OBJECTIVE: To conduct a systematic review and quantitatively assess whether the usage of GLP-1RA is associated with the increased risk of having depression-related adverse events and to learn more about the sources of heterogeneity. METHODS: In accordance with the PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, and LILACS for randomized controlled trials and observational studies published between 2000 and 2025. Studies were eligible if they enrolled adults with overweight or obesity and reported outcomes related to depression or mood. Random-effects models were used for meta-analysis, with heterogeneity, sensitivity analysis, meta-regression, and publication bias assessments conducted. RESULTS: A total of 19 studies were included in this systematic review. Combined findings revealed that the risk of depression was linked to the utilization of GLP-1RA (OR = 1.49, 95% CI: 1.18–1.88). Between-study heterogeneity was very high (I² = 99.21%) although sensitivity analysis revealed that the findings were robust. The heterogeneity was not explained by a…
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