THE DISCONTINUATION of glucagon-like peptide-1 (GLP-1) receptor agonists is tied to an increased risk of psychiatric events in people with Type 2 diabetes, according to a new cohort study.1
Comparing GLP-1s with DPP4 and SGLT2 Inhibitors
Findings around the psychiatric safety profile of GLP-1 receptor agonists remain inconsistent during treatment and largely unknown after discontinuation, authors highlighted.
Previous research has found that during treatment with GLP-1s, patients with major depressive disorder can experience improved measures of motivation.2
Researchers used large-scale electronic health records from the Shanghai Hospital Link Database to investigate incident depressive and anxiety disorders during treatment with GLP-1 receptor agonists, as well as after its discontinuation in patients with Type 2 diabetes.1
This was in comparison to to dipeptidyl peptidase-4 (DPP4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors.
During Treatment
During active treatment, GLP-1 receptor agonists showed no heightened risk of psychiatric events compared with DPP4 inhibitors.
Previous research supports, with a 2025 study finding no association between active treatment with GLP-1s and adverse psychiatric events.3
GLP-1s showed a lower risk of psychiatric events during treatment than SGLT2 inhibitors.1
After Treatment Discontinuation
However, after treatment cessation, prior use of GLP-1 receptor agonists was an indicator of the patient being at higher risk of psychiatric events, compared with both DPP4 and SGLT2 inhibitors.
The increase in risk was modestly mediated by elevated triglyceride levels.
Clinical Implications
Researchers highlighted the need for clinical vigilance regarding anxiety disorders following discontinuation of treatment with GLP-1 receptor agonists in patients with Type 2 diabetes.
References
1 Zhang T et al. Association of GLP-1RA discontinuation and risk of depressive and anxiety disorders in people with Type 2 diabetes: a cohort study. Nat Metab. 2026;DOI:10.1038/s42255-026-01567-z.
2 Gill H et al. Semaglutide and effort-based decision-making in major depressive disorder: a randomised clinical trial. 2026;DOI:10.1001/jamapsychiatry.2026.0594.
3 Pierret ACS et al. Glucagon-like peptide 1 receptor agonists and mental health: a systematic review and meta-analysis. JAMA Psychiatry. 2025;82(7):643–653.
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