Glucagon-like peptide-1 receptor agonists risk for anxiety and depression risk, and suicidality: a large cohort study

Jan 27, 2026Diabetes research and clinical practice

Risk of anxiety, depression, and suicidal thoughts with glucagon-like peptide-1 receptor agonist use in a large group

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Abstract

Among 100,500 patients, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i and DPP4i.

GLP-1 RAs showed a higher risk of depression compared to SGLT2i (HR 1.19) and DPP4i (HR 1.06).
Anxiety disorder risk was also higher for GLP-1 RAs compared to SGLT2i (HR 1.09) and DPP4i (HR 1.07).
There was no significant difference in suicidality risk between GLP-1 RAs and SU.
GLP-1 RAs were associated with a lower risk of suicidal ideation compared to SU (HR 0.62).

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AIMS: This study examines the incidence of anxiety, depression, and suicidality after treatment initiation with antihyperglycemic mediations in patients with type 2 diabetes (T2D) which 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: Among 100,500 patients, 16,424 started using GLP-1 RAs, 13,855 SGLT2i, 27,614 DPP4i, and 42,607 SU. 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 are associated with higher risk of anxiety and depression but no difference in suicidality and self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU.

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Glucagon-like peptide-1 receptor agonists risk for anxiety and depression risk, and suicidality: a large cohort study

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