Association Between Baseline Glucagon-like Peptide-1 Receptor Agonist Use and Newly Documented Depression Diagnosis in Adults with Type 2 Diabetes: A Multi-State Medicaid Cohort Study

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus (T2DM). However, its mental health safety profile in routine care, particularly among Medicaid beneficiaries, remains uncertain. We aim to examine the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and newly documented depression diagnosis among adults with type 2 diabetes mellitus (T2DM) enrolled in Medicaid. Methods: We conducted a retrospective longitudinal cohort study using the 2022–2023 Merative™ MarketScan® Multi-State Medicaid Database. Adults aged 18–64 years with T2DM, continuous Medicaid enrollment, and no documented depression during the 2022 baseline period were included. Baseline GLP-1 RA use was assessed in 2022, and newly diagnosed depression was identified in 2023. Associations were estimated using multivariable logistic regression, inverse probability weighting (IPW), and a doubly robust estimator. Results: Among 74,760 eligible adults, 14,953 (20.0%) were GLP-1 RA users. Incident depression occurred in 12.9% of users and 11.1% of non-users (absolute difference, 1.8 percentage points; p < 0.001). GLP-1 RA use was associated with higher odds of newly documented depression diagnosis in multivariable analysis (adjusted OR 1.10, 95% CI 1.04–1.16), IPW analysis (OR 1.09, 95% CI 1.03–1.15), and doubly robust analysis (OR 1.09, 95% CI 1.03–1.15). Conclusions: Baseline GLP-1 RA use was associated with modestly higher odds of a newly documented depression diagnosis during the subsequent year. Prospective studies are needed to determine whether this association is causal.