Presentation (CTI)

OBJECTIVES: Regulatory agencies have raised concerns about potential psychiatric adverse effects of GLP-1 receptor agonists (GLP-1RA). While several studies have demonstrated a null association with suicidality, evidence regarding broader psychiatric outcomes remains limited.
METHODS: We conducted a retrospective cohort study using MarketScan (2015-2022). Two populations were defined: adults with type 2 diabetes (T2D) and adults treated for overweight/obesity. Within each population, we identified new users of GLP-1RA and comparator medications commonly used for the same indication (SGLT2i and DPP-4i in T2D; phentermine-topiramate and naltrexone-bupropion in obesity). Inverse probability of treatment weighting was used to adjust for ~50 baseline covariates. The primary outcome was a composite of incident depression, anxiety, or insomnia. Secondary outcomes included psychiatric hospitalization, suicide attempt, and nonfatal self-harm events, and individual components of the primary outcome.
RESULTS: Among 493,404 weighted adults with T2D (mean age, 52 years; 42% female), initiation of GLP-1RA conferred a marginally increased risk of the composite psychiatric outcome compared with SGLT2i (HR, 1.14; 95% CI, 1.11-1.18), and a small but a significant increase in risk compared with DPP-4i (HR, 1.04; 95% CI, 1.01-1.07). Among 110,977 adults treated for obesity, GLP-1RA use showed no significant difference versus phentermine-topiramate (HR 0.88, 95% CI 0.74, 1.05) and a numerically higher but non-significant risk versus naltrexone-bupropion (HR 1.19, 95% CI 0.84, 1.69). Across both populations, no increased risk of severe secondary psychiatric outcomes, including suicidality, was observed.
CONCLUSIONS: Overall, psychiatric risk with GLP-1RA was modest and varied by indication and comparator; among adults treated for obesity, no significant associations were observed, though small risk increases cannot be excluded.