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Tagliapietra GA, Cantrell MA, Lund BC. Glucagon-like peptide receptor agonists and risk for depression. Primary Care Diabetes. 2024 Jun 7.
AIMS: Package labeling for weight loss formulations of semaglutide and liraglutide include a warning for suicidal thoughts and behaviors. The objective was to examine the association between glucagon-like peptide-1 receptor agonists (GLP-1RA) and incident depression. METHODS: This retrospective cohort study compared Veterans Health Administration patients initiated on a GLP-1RA versus a dipeptidyl peptidase-4 inhibitor (DPP-4i) between June 1, 2013 and June 30, 2020. The primary outcome was incident depression, defined as a new diagnosis of depression or new antidepressant prescription, within 1 year following drug initiation. Multivariable log-binomial regression was used to estimate relative risk, adjusted for confounding factors including patient demographics, comorbid conditions, and prior medication. RESULTS: Of 34,130 patients initiated on a GLP-1RA and 105,478 initiated on a DPP-4i, incident depression occurred in 7.7?% (n = 2263) and 6.3?% (n = 6602), respectively. After adjustment, the relative risk was 1.02 (95?% CI: 0.97 - 1.07), thus failing to demonstrate a significant increase in risk for incident depression following initiation of a GLP-1RA compared to DPP-4i. Relative risk estimates in all sensitivity analyses were also non-significant. CONCLUSIONS: This study did not demonstrate a significant increase in risk for incident depression following GLP-1RA initiation.