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<p>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.</p>

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Association of GLP-1RA discontinuation and risk of depressive and anxiety disorders in people with type 2 diabetes: a cohort study

  • 期刊论文

  • 发表日期：

    2026年7月9日

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  • Tingyu Zhang,
  • Ping He,
  • Yunxi Ji,
  • Juan Shi,
  • Zizheng Zhang,
  • Kan Wang,
  • Haolei Pan,
  • Huayan Yao,
  • Yanbin Xue,
  • Ruizhi Zheng,
  • Qingxia Wu,
  • Bin Cui,
  • Yifei Zhang,
  • Weiqing Wang,
  • Guang Ning

摘要

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.