Association of glucagon-like peptide-1 receptor agonist use with anxiety disorders, depression, self-harm, and suicidality: a large cohort study

Abstract

Aims: This study examines the incidence of anxiety disorders, depression, self-harm, and suicidality after treatment initiation with antihyperglycemic medications in patients with type 2 diabetes (T2D) who take metformin as first-line treatment.

Methods: A large cohort study was conducted using TriNetX electronic health records andincluded adults (≥18 years) with T2D who used metformin and initiated GLP-1 RAs, SGLT2i, DPP4i, or SU between 1 April 2013 and 31 December 2019.

Results: The final three propensity-matched cohorts were 1) GLP-1 RA vs DPP4i (n = 28,536), 2) GLP-1 RA vs SU (n = 23,486), and 3) GLP-1 RA vs SGLT2i (n = 24,052). In a median follow-up of 5.5 years, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i (HR 1.19, 95% CI 1.11-1.28), and DPP4i (HR 1.06, 95% CI 1.00-1.13) but not SU. Anxiety disorder risk was also higher for GLP-1 RAs versus SGLT2i (HR 1.09, 95% CI 1.02- 1.16) and DPP4i (HR 1.07, 95% CI 1.02-1.13) but not SU. On the contrary, GLP-1 RAs were associated with a lower risk for suicidal ideation in comparison with SU (HR 0.62, 95% CI 0.44-0.87).

Conclusions: GLP-1 RAs were associated with a higher risk of anxiety disorders and depression, but no difference in suicidality or self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU.

Keywords: Antihyperglycemic medications; Anxiety disorders; Depression; GLP-1RAs; Psychiatric outcomes; Self-harm; Suicidality; Type 2 diabetes.