Nature metabolismJul 9, 2026

Stopping GLP-1RA treatment linked to higher risk of depression and anxiety in people with type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 10, 2026

Abstract

GLP-1RA discontinuation is associated with an increased risk of psychiatric events.

During treatment, GLP-1RAs show a neutral risk of psychiatric events compared to DPP4is.
GLP-1RAs are associated with a lower risk of psychiatric events compared to SGLT2is during treatment.
After discontinuation, prior use of GLP-1RAs is linked to a higher risk of depressive and anxiety disorders than DPP4is or SGLT2is.
Elevated triglyceride levels may modestly mediate the increased risk of psychiatric events after GLP-1RA cessation.
These findings suggest the importance of monitoring for anxiety following the discontinuation of GLP-1RAs.

Simplified

The psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is characterized by inconsistent findings during active treatment and remains largely unexplored after cessation. Here we show that GLP-1RA discontinuation is associated with an increased risk of psychiatric events. Using large-scale electronic health records from the Shanghai Hospital Link Database, we investigate incident depressive and anxiety disorders during GLP-1RA treatment and after its discontinuation in people with type 2 diabetes, compared with dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium-glucose cotransporter-2 inhibitors (SGLT2is). During treatment, GLP-1RAs show a neutral risk compared with DPP4is and a lower risk compared with SGLT2is. In contrast, after cessation, prior use of GLP-1RAs is associated with a higher risk than prior use of DPP4is or SGLT2is. This increase is modestly mediated by elevated triglyceride levels. These findings highlight the need for clinical vigilance regarding anxiety following GLP-1RA discontinuation.